Patricia Buckendahl | Rutgers, The State University of New Jersey (original) (raw)
Papers by Patricia Buckendahl
PubMed, Dec 1, 2000
The aim of this experiment was to identify the location of the biochemical changes associated wit... more The aim of this experiment was to identify the location of the biochemical changes associated with depressed mineralization during space flight. We carried out biochemical analysis of 4 sections of the femoral diaphyses from 107 day old male rats flown aboard Cosmos 2044 Biosatellite for 16 days. Control femurs were preflight, vivarium, synchronous for feed, cage and temperature exposure, and a flight simulation model. Distal sections in both the flight and synchronous femurs showed mineral deficits associated with reduced levels of the reducible cross-link product of type I collagen, dehydro-dihydroxylysinonorleucine (deH-DHLNL) (p<.05). Unloaded bones in the ground based flight simulation model showed changes in cross-links similar to flight and synchronous controls, but were not associated with the mineral deficit. Mean values of elements measured in each section of all groups revealed significant associations (p<.005) between the non-collagenous protein, osteocalcin and calcium (r=0.774), phosphorus (r=-.624) and deH-DHLNL/deH-HLNL (r=.883). The ratio of the nonreducible cross-link, pyridinoline, to its lysl analogue, deoxypyridinoline, was consistently lower in the distal than proximal sections of the groups tested. None of the changes during space flight were unique to flight bone. The most significant and extensive changes in bone composition, i.e. mineral deficits associated with changes in both osteocalcin and reducible cross-links, were located in the distal section of the diaphysis of the femur.
Previous analyses of the composition of min(a'al and matrix in the bone of young rats following s... more Previous analyses of the composition of min(a'al and matrix in the bone of young rats following space _ght has revealed deficits in caldum,_ and oslcocalcin, a non-collagenous protein,without an associated _ in collagen. To dmractefi_ the location and natureof this mineralization defect in a wtught bearinglong bone, the fenlu', we attemptedto relate the spatial disuibution of mineral in_tu in the proximal, central and distal thirdsof the femoral diaphysis to the biochemical composition of bone from the same;areas. Biochemical analyses revealed lower concentrations of calcium, phosphorusand osteocalcin but not coHegenonly in the _nual thirdof the diaphysis of the flight animals (F) compm'_ ;o synchronouscontrols (S). Collagen concentration was reduced only hi the _ thixclof the diaphysis, where all 3 crosslink_ expressed as nM/moi collagen, were higher in F than S. A new technique, X-ray micro. tomography, with a resolutionof 26 microns, was used to obtain semi quantitativedam on mineral distributionin reconstructedsections of-,vet whole bone. To ingn_v¢ the resolution of the mineral density distribution, images of the surfaces of cut sections were analyzed by bac_ electrons in a scanning electron microscope (BSE). There was good agreement between the results _. of the twostereocbemical techniques which _vealed distinct patternsof mineralization in _ transve:se and longimd/nal directions of the diaphysis. The longi:udinal grad/ent in miaeral concentrations in the proximal two-thirdsof the diaphysis compared well with the semiquantitatlve estimates from the microtomography study in F and S. Correlationof mineral concentrations and BSE patternsadded a new dimension to our knowledge of the changes in " distribution of mineral most vulnerableto the environmentaleffects in this experiment. Circulatingparametersof skeletal metabolism revealeddiff_ences in serum-alcium, osteocalcin and alkaline phosphatase,suggestive of sT_-roid hormone excess in the flight animals. These findings, the reduced body weight and enlarged adrenal glands of the flight animals, possibly due to post flight environmental stress, precludeany interpretationof oar results with reference to space flight pet"se. Nevertheless, the novel methodology developed for this flight experiment shows considerable promise in elucidating the biochemical natme of what appear to be regional alterations in the mineralization of long bones of animals exposed to spaceflight.
Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology, 2000
ABSTRACT The calcium endocrine system regulates the supply of calcium and phosphorus for the mine... more ABSTRACT The calcium endocrine system regulates the supply of calcium and phosphorus for the mineralization of bone, a process that is known to be depressed during spaceflight. The role of circulating hormones in the localized decrease in bone formation in the weight-bearing skeleton is unresolved and difficult to study in the human because of the effects of exercise itself on calcium metabolism. Additional knowledge would not only improve understanding of the mechanism of adaptation to a weightless environment, but also provide a rationale for the use of the hormones of the calcium endocrine system-parathyroid hormone, calcitonin, and the vitamin D hormone (1,25-D)-in the prevention or restoration of bone loss during spaceflight. Currently, therapeutic trials that include these hormones are under way for the human osteoporoses that can result from systemic factors such as estrogen deficiency.
PubMed, Dec 1, 1985
To test the husbandry capabilities of the Research Animal Holding Facility (RAHF) during space fl... more To test the husbandry capabilities of the Research Animal Holding Facility (RAHF) during space flight, 24 male rats were flown on Spacelab 3 for 7 days. Twelve large rats (400 g, LF), 5 of which had telemetry devices implanted (IF), and 12 small rats (200 g, SF) were housed in the RAHF. Examination 3 hr after landing (R + 3) revealed the rats to be free of injury, well nourished, and stained with urine. At R + 10 the rats were lethargic and atonic with hyperemia of the extremities and well groomed except for a middorsal area stained with urine and food. Both LF and SF rats showed weight gains comparable to their IG controls; IF rats grew less than controls. Food and water consumption were similar for flight and control groups. Plasma concentrations of total protein, sodium, albumin and creatinine did not differ between flight and control groups. LF and SF rats had elevated plasma glucose, and SF rats had increased blood urea nitrogen, potassium and glutamic pyruvic transaminase. These observations indicate that rats maintained in the RAHF were healthy, well nourished and experienced minimal stress; physiological changes in the rats can thus be attributed to the effects of space flight.
Frontiers in Pharmacology, Jun 21, 2022
Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammatio... more Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammation, and increased risk of cardiometabolic disease and osteoporosis. The riskbenefit profile of hormone replacement therapy is not favorable in postmenopausal women therefore better treatment options are needed. Cannabidiol (CBD), a non-psychotropic phytocannabinoid extracted from hemp, has shown pharmacological activities suggesting it has therapeutic value for postmenopause, which can be modeled in ovariectomized (OVX) mice. We evaluated the efficacy of cannabidiol (25 mg/kg) administered perorally to OVX and sham surgery mice for 18 weeks. Compared to VEH-treated OVX mice, CBDtreated OVX mice had improved oral glucose tolerance, increased energy expenditure, improved whole body areal bone mineral density (aBMD) and bone mineral content as well as increased femoral bone volume fraction, trabecular thickness, and volumetric bone mineral density. Compared to VEH-treated OVX mice, CBD-treated OVX mice had increased relative abundance of fecal Lactobacillus species and several gene expression changes in the intestine and femur consistent with reduced inflammation and less bone resorption. These data provide preclinical evidence supporting further investigation of CBD as a therapeutic for postmenopause-related disorders.
The Journal of Steroid Biochemistry and Molecular Biology
Comparative Biochemistry and Physiology Part A: Physiology, 1994
The development of pineal function in northern elephant seals was examined in an attempt to under... more The development of pineal function in northern elephant seals was examined in an attempt to understand the physiological basis for previously observed high daytime levels of melatonin in neonatal southern elephant seals. Pineal glands from four northern elephant seal pups, estimated age less than 1 week, weighed 3.0 + 0.80 g, which was significantly less than that previously found in southern elephant seals (4.6 f 0.35 g). Midday concentrations of plasma melatonin in pups averaged more than 3000 pmol/l in the first 5 days post-partum, but declined rapidly to less than 400 pmol/l after day 9. Daytime melatonin levels in northern elephant seals tended to be lower than in southern elephant seals, although they were very high compared with other species. A circadian cycle of plasma melatonin concentration was observed in newborn northern elephant seals, with levels of 3000-5000 pmol/l during the day, rising to more than 10,000 pmol/l late in the dark phase. Soon after weaning at 4 weeks of age, daytime and night-time levels were in the range 60-100 pmol/l and 100-400 pmol/l, respectively. When approximately 10 weeks old, most samples were in the range 100-400 pmol/l with no discernible difference between day and night levels. The results do not support the hypothesis that the pineal gland is involved in thermogenesis in newborn southern elephant seals. Instead, the very active pineal gland may contribute to energy conservation, by lowering body temperature, particularly at night. As physical insulation is acquired by the deposition of blubber, the mechanism is not required and melatonin falls to adult levels.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1988
Decreased bone formation in rats during spaceflight may be attributable to corticosteroid excess ... more Decreased bone formation in rats during spaceflight may be attributable to corticosteroid excess induced by environmental factors other than weightlessness that are associated with spaceflight experiments. To determine whether decreased osteocalcin, which may reflect altered bone formation rate, could be associated with corticosteroid excess, we measured serum osteocalcin in rats after injection of corticosterone or in response to various environmental stimuli. Exogenous steroid elicited a time- and dose-related decrease in serum osteocalcin, which was significant within 1 h of administration and maximally 25% below controls 1.5 h after injection of 3.3 mg corticosterone/kg body wt, the highest dose we tested. Adrenalectomy resulted in a 38% increase in osteocalcin. Exposure to environmental stressors lasting from 1.5 h to 3 wk also resulted in decreased osteocalcin levels, which showed a strong negative correlation (P less than 0.001) with serum corticosterone levels and adrenal ma...
Journal of the Mechanical Behavior of Biomedical Materials, 2009
In healthy bone there is a balance between bone resorption and formation. When an imbalance occur... more In healthy bone there is a balance between bone resorption and formation. When an imbalance occurs there is an overall loss of bone mass leading to an increased risk of fracture. The deterioration is typically accompanied by changes in the non-collagenous proteins in the bone. Osteocalcin (OC) is the most abundant noncollageneous bone matrix protein and it is believed to play a role in bone formation and resorption. Nanoindentation and Raman microspectroscopy have been used to correlate the mechanical and chemical properties of cortical bone from femora of OC−/− (osteocalcin deficient) mice and their wild-type controls (OC+/+). There are significant intra-bone variations in mechanics and crystallinity especially in the mid-cortical section for OC−/− mice compared to OC+/+ mice. Type-B carbonate substitution decreased significantly in the absence of osteocalcin and this appears to affect the hardness more than the elasticity. The results suggest that OC plays a role in the growth of apatite crystals in bone by increasing the degree of carbonate substitutions. The addition of these defects to the apatite's crystal lattice has little effect on elasticity, but does appear to reduce the bone's hardness.
Frontiers in Pharmacology
Frontiers in Pharmacology
Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammatio... more Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammation, and increased risk of cardiometabolic disease and osteoporosis. The risk-benefit profile of hormone replacement therapy is not favorable in postmenopausal women therefore better treatment options are needed. Cannabidiol (CBD), a non-psychotropic phytocannabinoid extracted from hemp, has shown pharmacological activities suggesting it has therapeutic value for postmenopause, which can be modeled in ovariectomized (OVX) mice. We evaluated the efficacy of cannabidiol (25 mg/kg) administered perorally to OVX and sham surgery mice for 18 weeks. Compared to VEH-treated OVX mice, CBD-treated OVX mice had improved oral glucose tolerance, increased energy expenditure, improved whole body areal bone mineral density (aBMD) and bone mineral content as well as increased femoral bone volume fraction, trabecular thickness, and volumetric bone mineral density. Compared to VEH-treated OVX mice, CBD-tre...
Nutrition Research
Obesity induced by high-fat diets (HFDs) is inversely associated with vitamin D status and bone h... more Obesity induced by high-fat diets (HFDs) is inversely associated with vitamin D status and bone health. However, the associations and effects of excessive fat intake on hepatic and renal vitamin D metabolism have not been addressed. The primary objective was to determine if excessive energy and fat intake, or the type of fat, affects serum 25-hydroxycholecalciferol concentration and whether this can be explained by an alteration of vitamin D-regulating enzymes in older mice. The second objective was a follow up of our recent findings that a high intake of monounsaturated fatty acids (MUFA) is not detrimental to bone in lean mice and whether this is also true under conditions of diet-induced obesity. In the study, twenty-one 8-month-old female C57BL/6 J mice were fed ad libitum for 10 weeks with a 10% normal-fat diet (NFD) or 45% HFD enriched with MUFA or saturated fatty acids (SFA). We found that the HFD, compared with NFD, resulted in greater energy intake, weight gain, total body fat, and liver fat (P < .05). Only the high SFA feeding resulted in higher mRNA but lower protein abundance of hepatic Cyp2r1 and lower renal Cyp24a1 mRNA expression than the NFD group (P < .05). Moreover, although bone mineral density did not differ among groups, the percent difference compared with NFD was significantly lower for SFA (P < .05) but not MUFA. Also, femoral trabecular bone volume fraction was lower (P < .05) only in the SFA compared with the NFD group. In conclusion, high SFA and MUFA feeding differentially affected gene and protein expressions of major vitamin D hydroxylases compared with NFD, but this was unrelated to the lower circulating 25-hydroxycholecalciferol concentration. In addition, only the SFA diet alters vitamin D metabolism and bone changes, indicating the importance of dietary fat composition.
Cellular and Molecular Neurobiology
Osteocalcin (OC) is an abundant extracellular calcium-binding protein synthesized by osteoblasts.... more Osteocalcin (OC) is an abundant extracellular calcium-binding protein synthesized by osteoblasts. Although most OC is bound to hydroxyapatite mineral during bone formation, a consistent amount is released directly to circulation. Plasma OC (pOC) levels are highly sensitive to stressful stimuli that alter stress-responsive hormones, such as glucocorticoids (cortisol or corticosterone) and the catecholamines norepinephrine and epinephrine. To gain a better understanding of the apparent relationship of OC to the effects of ethanol (EtOH) and the stress responses, we compared mice that have OC (WT [OC+/+] and HET [OC+/-]) with OC null mutants (KO [OC-/-]), which have no OC in either plasma or in bone. One experiment included chronic unpredictable stress, a second was conducted in the absence of any known stressors other than EtOH, while a third imposed a more severe acute immobilization stress in addition to EtOH consumption. The data obtained confirmed significant differences in EtOH consumption in mice that previously experienced various stressful stimuli. We also determined that adrenal tyrosine-hydroxylase expression was inversely proportional to EtOH consumption and tended to be lower in KO than in WT. Data suggest that OC possesses the ability to modulate the adrenal gene expression of the catecholamine synthetic pathway. This modulation may be responsible for differences in EtOH consumption under stress.
The American journal of physiology
ABSTRACT
Journal of Experimental Biology, 2015
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1990
We combined biochemical measurements with novel techniques for image analysis in the rat femur to... more We combined biochemical measurements with novel techniques for image analysis in the rat femur to characterize the location and nature of the defect in mineralization known to occur in growing animals after spaceflight. Concentrations of mineral and osteocalcin were low in the distal half of the diaphysis and concentrations of collagen were low with evidence of increased synthesis in the proximal half of the diaphysis of the flight bones. X-ray microtomography provided semiquantitative data in computer-generated sections of whole wet bone that indicated a longitudinal gradient of decreasing mineralization toward the distal diaphysis, similar to the chemistry results. Analysis of embedded sections by backscattered electrons in a scanning electron microscope revealed distinct patterns of mineral distribution in the proximal, central, and distal regions of the diaphysis and also showed a net reduction in mineral levels toward the distal shaft. Increases in mineral density to higher fra...
American journal of physiology. Regulatory, integrative and comparative physiology, 2001
We previously showed that psychological stressors alter plasma levels of osteocalcin (pOC), a bon... more We previously showed that psychological stressors alter plasma levels of osteocalcin (pOC), a bone-specific mineral binding protein, in ways that differ with the type of stressor. To determine effects of chronic stress, we examined vertebrae, pOC, and corticosterone levels from conscious rats subjected to foot-restraint immobilization (Immo) daily for 1-42 times. After 40-42 Immo, basal pOC was decreased by 25% compared with unstressed rats, and the subsequent rise in pOC during Immo was blunted. Corticosterone was elevated 10-fold during Immo. Immo for seven times did not change vertebral OC concentration, but caused a slight decrease in calcium and phosphorous concentrations in younger rats. Rats Immo for 42 times exhibited reduced body weight, vertebral weight, and vertebral OC concentration but no significant differences in vertebral mineral concentrations. Body fat content was visibly decreased. We do not know the source of or the stimulus for the initial rise in pOC. We conclu...
PubMed, Dec 1, 2000
The aim of this experiment was to identify the location of the biochemical changes associated wit... more The aim of this experiment was to identify the location of the biochemical changes associated with depressed mineralization during space flight. We carried out biochemical analysis of 4 sections of the femoral diaphyses from 107 day old male rats flown aboard Cosmos 2044 Biosatellite for 16 days. Control femurs were preflight, vivarium, synchronous for feed, cage and temperature exposure, and a flight simulation model. Distal sections in both the flight and synchronous femurs showed mineral deficits associated with reduced levels of the reducible cross-link product of type I collagen, dehydro-dihydroxylysinonorleucine (deH-DHLNL) (p<.05). Unloaded bones in the ground based flight simulation model showed changes in cross-links similar to flight and synchronous controls, but were not associated with the mineral deficit. Mean values of elements measured in each section of all groups revealed significant associations (p<.005) between the non-collagenous protein, osteocalcin and calcium (r=0.774), phosphorus (r=-.624) and deH-DHLNL/deH-HLNL (r=.883). The ratio of the nonreducible cross-link, pyridinoline, to its lysl analogue, deoxypyridinoline, was consistently lower in the distal than proximal sections of the groups tested. None of the changes during space flight were unique to flight bone. The most significant and extensive changes in bone composition, i.e. mineral deficits associated with changes in both osteocalcin and reducible cross-links, were located in the distal section of the diaphysis of the femur.
Previous analyses of the composition of min(a'al and matrix in the bone of young rats following s... more Previous analyses of the composition of min(a'al and matrix in the bone of young rats following space _ght has revealed deficits in caldum,_ and oslcocalcin, a non-collagenous protein,without an associated _ in collagen. To dmractefi_ the location and natureof this mineralization defect in a wtught bearinglong bone, the fenlu', we attemptedto relate the spatial disuibution of mineral in_tu in the proximal, central and distal thirdsof the femoral diaphysis to the biochemical composition of bone from the same;areas. Biochemical analyses revealed lower concentrations of calcium, phosphorusand osteocalcin but not coHegenonly in the _nual thirdof the diaphysis of the flight animals (F) compm'_ ;o synchronouscontrols (S). Collagen concentration was reduced only hi the _ thixclof the diaphysis, where all 3 crosslink_ expressed as nM/moi collagen, were higher in F than S. A new technique, X-ray micro. tomography, with a resolutionof 26 microns, was used to obtain semi quantitativedam on mineral distributionin reconstructedsections of-,vet whole bone. To ingn_v¢ the resolution of the mineral density distribution, images of the surfaces of cut sections were analyzed by bac_ electrons in a scanning electron microscope (BSE). There was good agreement between the results _. of the twostereocbemical techniques which _vealed distinct patternsof mineralization in _ transve:se and longimd/nal directions of the diaphysis. The longi:udinal grad/ent in miaeral concentrations in the proximal two-thirdsof the diaphysis compared well with the semiquantitatlve estimates from the microtomography study in F and S. Correlationof mineral concentrations and BSE patternsadded a new dimension to our knowledge of the changes in " distribution of mineral most vulnerableto the environmentaleffects in this experiment. Circulatingparametersof skeletal metabolism revealeddiff_ences in serum-alcium, osteocalcin and alkaline phosphatase,suggestive of sT_-roid hormone excess in the flight animals. These findings, the reduced body weight and enlarged adrenal glands of the flight animals, possibly due to post flight environmental stress, precludeany interpretationof oar results with reference to space flight pet"se. Nevertheless, the novel methodology developed for this flight experiment shows considerable promise in elucidating the biochemical natme of what appear to be regional alterations in the mineralization of long bones of animals exposed to spaceflight.
Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology, 2000
ABSTRACT The calcium endocrine system regulates the supply of calcium and phosphorus for the mine... more ABSTRACT The calcium endocrine system regulates the supply of calcium and phosphorus for the mineralization of bone, a process that is known to be depressed during spaceflight. The role of circulating hormones in the localized decrease in bone formation in the weight-bearing skeleton is unresolved and difficult to study in the human because of the effects of exercise itself on calcium metabolism. Additional knowledge would not only improve understanding of the mechanism of adaptation to a weightless environment, but also provide a rationale for the use of the hormones of the calcium endocrine system-parathyroid hormone, calcitonin, and the vitamin D hormone (1,25-D)-in the prevention or restoration of bone loss during spaceflight. Currently, therapeutic trials that include these hormones are under way for the human osteoporoses that can result from systemic factors such as estrogen deficiency.
PubMed, Dec 1, 1985
To test the husbandry capabilities of the Research Animal Holding Facility (RAHF) during space fl... more To test the husbandry capabilities of the Research Animal Holding Facility (RAHF) during space flight, 24 male rats were flown on Spacelab 3 for 7 days. Twelve large rats (400 g, LF), 5 of which had telemetry devices implanted (IF), and 12 small rats (200 g, SF) were housed in the RAHF. Examination 3 hr after landing (R + 3) revealed the rats to be free of injury, well nourished, and stained with urine. At R + 10 the rats were lethargic and atonic with hyperemia of the extremities and well groomed except for a middorsal area stained with urine and food. Both LF and SF rats showed weight gains comparable to their IG controls; IF rats grew less than controls. Food and water consumption were similar for flight and control groups. Plasma concentrations of total protein, sodium, albumin and creatinine did not differ between flight and control groups. LF and SF rats had elevated plasma glucose, and SF rats had increased blood urea nitrogen, potassium and glutamic pyruvic transaminase. These observations indicate that rats maintained in the RAHF were healthy, well nourished and experienced minimal stress; physiological changes in the rats can thus be attributed to the effects of space flight.
Frontiers in Pharmacology, Jun 21, 2022
Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammatio... more Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammation, and increased risk of cardiometabolic disease and osteoporosis. The riskbenefit profile of hormone replacement therapy is not favorable in postmenopausal women therefore better treatment options are needed. Cannabidiol (CBD), a non-psychotropic phytocannabinoid extracted from hemp, has shown pharmacological activities suggesting it has therapeutic value for postmenopause, which can be modeled in ovariectomized (OVX) mice. We evaluated the efficacy of cannabidiol (25 mg/kg) administered perorally to OVX and sham surgery mice for 18 weeks. Compared to VEH-treated OVX mice, CBDtreated OVX mice had improved oral glucose tolerance, increased energy expenditure, improved whole body areal bone mineral density (aBMD) and bone mineral content as well as increased femoral bone volume fraction, trabecular thickness, and volumetric bone mineral density. Compared to VEH-treated OVX mice, CBD-treated OVX mice had increased relative abundance of fecal Lactobacillus species and several gene expression changes in the intestine and femur consistent with reduced inflammation and less bone resorption. These data provide preclinical evidence supporting further investigation of CBD as a therapeutic for postmenopause-related disorders.
The Journal of Steroid Biochemistry and Molecular Biology
Comparative Biochemistry and Physiology Part A: Physiology, 1994
The development of pineal function in northern elephant seals was examined in an attempt to under... more The development of pineal function in northern elephant seals was examined in an attempt to understand the physiological basis for previously observed high daytime levels of melatonin in neonatal southern elephant seals. Pineal glands from four northern elephant seal pups, estimated age less than 1 week, weighed 3.0 + 0.80 g, which was significantly less than that previously found in southern elephant seals (4.6 f 0.35 g). Midday concentrations of plasma melatonin in pups averaged more than 3000 pmol/l in the first 5 days post-partum, but declined rapidly to less than 400 pmol/l after day 9. Daytime melatonin levels in northern elephant seals tended to be lower than in southern elephant seals, although they were very high compared with other species. A circadian cycle of plasma melatonin concentration was observed in newborn northern elephant seals, with levels of 3000-5000 pmol/l during the day, rising to more than 10,000 pmol/l late in the dark phase. Soon after weaning at 4 weeks of age, daytime and night-time levels were in the range 60-100 pmol/l and 100-400 pmol/l, respectively. When approximately 10 weeks old, most samples were in the range 100-400 pmol/l with no discernible difference between day and night levels. The results do not support the hypothesis that the pineal gland is involved in thermogenesis in newborn southern elephant seals. Instead, the very active pineal gland may contribute to energy conservation, by lowering body temperature, particularly at night. As physical insulation is acquired by the deposition of blubber, the mechanism is not required and melatonin falls to adult levels.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1988
Decreased bone formation in rats during spaceflight may be attributable to corticosteroid excess ... more Decreased bone formation in rats during spaceflight may be attributable to corticosteroid excess induced by environmental factors other than weightlessness that are associated with spaceflight experiments. To determine whether decreased osteocalcin, which may reflect altered bone formation rate, could be associated with corticosteroid excess, we measured serum osteocalcin in rats after injection of corticosterone or in response to various environmental stimuli. Exogenous steroid elicited a time- and dose-related decrease in serum osteocalcin, which was significant within 1 h of administration and maximally 25% below controls 1.5 h after injection of 3.3 mg corticosterone/kg body wt, the highest dose we tested. Adrenalectomy resulted in a 38% increase in osteocalcin. Exposure to environmental stressors lasting from 1.5 h to 3 wk also resulted in decreased osteocalcin levels, which showed a strong negative correlation (P less than 0.001) with serum corticosterone levels and adrenal ma...
Journal of the Mechanical Behavior of Biomedical Materials, 2009
In healthy bone there is a balance between bone resorption and formation. When an imbalance occur... more In healthy bone there is a balance between bone resorption and formation. When an imbalance occurs there is an overall loss of bone mass leading to an increased risk of fracture. The deterioration is typically accompanied by changes in the non-collagenous proteins in the bone. Osteocalcin (OC) is the most abundant noncollageneous bone matrix protein and it is believed to play a role in bone formation and resorption. Nanoindentation and Raman microspectroscopy have been used to correlate the mechanical and chemical properties of cortical bone from femora of OC−/− (osteocalcin deficient) mice and their wild-type controls (OC+/+). There are significant intra-bone variations in mechanics and crystallinity especially in the mid-cortical section for OC−/− mice compared to OC+/+ mice. Type-B carbonate substitution decreased significantly in the absence of osteocalcin and this appears to affect the hardness more than the elasticity. The results suggest that OC plays a role in the growth of apatite crystals in bone by increasing the degree of carbonate substitutions. The addition of these defects to the apatite's crystal lattice has little effect on elasticity, but does appear to reduce the bone's hardness.
Frontiers in Pharmacology
Frontiers in Pharmacology
Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammatio... more Loss of ovarian 17β-estradiol (E2) in postmenopause is associated with gut dysbiosis, inflammation, and increased risk of cardiometabolic disease and osteoporosis. The risk-benefit profile of hormone replacement therapy is not favorable in postmenopausal women therefore better treatment options are needed. Cannabidiol (CBD), a non-psychotropic phytocannabinoid extracted from hemp, has shown pharmacological activities suggesting it has therapeutic value for postmenopause, which can be modeled in ovariectomized (OVX) mice. We evaluated the efficacy of cannabidiol (25 mg/kg) administered perorally to OVX and sham surgery mice for 18 weeks. Compared to VEH-treated OVX mice, CBD-treated OVX mice had improved oral glucose tolerance, increased energy expenditure, improved whole body areal bone mineral density (aBMD) and bone mineral content as well as increased femoral bone volume fraction, trabecular thickness, and volumetric bone mineral density. Compared to VEH-treated OVX mice, CBD-tre...
Nutrition Research
Obesity induced by high-fat diets (HFDs) is inversely associated with vitamin D status and bone h... more Obesity induced by high-fat diets (HFDs) is inversely associated with vitamin D status and bone health. However, the associations and effects of excessive fat intake on hepatic and renal vitamin D metabolism have not been addressed. The primary objective was to determine if excessive energy and fat intake, or the type of fat, affects serum 25-hydroxycholecalciferol concentration and whether this can be explained by an alteration of vitamin D-regulating enzymes in older mice. The second objective was a follow up of our recent findings that a high intake of monounsaturated fatty acids (MUFA) is not detrimental to bone in lean mice and whether this is also true under conditions of diet-induced obesity. In the study, twenty-one 8-month-old female C57BL/6 J mice were fed ad libitum for 10 weeks with a 10% normal-fat diet (NFD) or 45% HFD enriched with MUFA or saturated fatty acids (SFA). We found that the HFD, compared with NFD, resulted in greater energy intake, weight gain, total body fat, and liver fat (P < .05). Only the high SFA feeding resulted in higher mRNA but lower protein abundance of hepatic Cyp2r1 and lower renal Cyp24a1 mRNA expression than the NFD group (P < .05). Moreover, although bone mineral density did not differ among groups, the percent difference compared with NFD was significantly lower for SFA (P < .05) but not MUFA. Also, femoral trabecular bone volume fraction was lower (P < .05) only in the SFA compared with the NFD group. In conclusion, high SFA and MUFA feeding differentially affected gene and protein expressions of major vitamin D hydroxylases compared with NFD, but this was unrelated to the lower circulating 25-hydroxycholecalciferol concentration. In addition, only the SFA diet alters vitamin D metabolism and bone changes, indicating the importance of dietary fat composition.
Cellular and Molecular Neurobiology
Osteocalcin (OC) is an abundant extracellular calcium-binding protein synthesized by osteoblasts.... more Osteocalcin (OC) is an abundant extracellular calcium-binding protein synthesized by osteoblasts. Although most OC is bound to hydroxyapatite mineral during bone formation, a consistent amount is released directly to circulation. Plasma OC (pOC) levels are highly sensitive to stressful stimuli that alter stress-responsive hormones, such as glucocorticoids (cortisol or corticosterone) and the catecholamines norepinephrine and epinephrine. To gain a better understanding of the apparent relationship of OC to the effects of ethanol (EtOH) and the stress responses, we compared mice that have OC (WT [OC+/+] and HET [OC+/-]) with OC null mutants (KO [OC-/-]), which have no OC in either plasma or in bone. One experiment included chronic unpredictable stress, a second was conducted in the absence of any known stressors other than EtOH, while a third imposed a more severe acute immobilization stress in addition to EtOH consumption. The data obtained confirmed significant differences in EtOH consumption in mice that previously experienced various stressful stimuli. We also determined that adrenal tyrosine-hydroxylase expression was inversely proportional to EtOH consumption and tended to be lower in KO than in WT. Data suggest that OC possesses the ability to modulate the adrenal gene expression of the catecholamine synthetic pathway. This modulation may be responsible for differences in EtOH consumption under stress.
The American journal of physiology
ABSTRACT
Journal of Experimental Biology, 2015
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1990
We combined biochemical measurements with novel techniques for image analysis in the rat femur to... more We combined biochemical measurements with novel techniques for image analysis in the rat femur to characterize the location and nature of the defect in mineralization known to occur in growing animals after spaceflight. Concentrations of mineral and osteocalcin were low in the distal half of the diaphysis and concentrations of collagen were low with evidence of increased synthesis in the proximal half of the diaphysis of the flight bones. X-ray microtomography provided semiquantitative data in computer-generated sections of whole wet bone that indicated a longitudinal gradient of decreasing mineralization toward the distal diaphysis, similar to the chemistry results. Analysis of embedded sections by backscattered electrons in a scanning electron microscope revealed distinct patterns of mineral distribution in the proximal, central, and distal regions of the diaphysis and also showed a net reduction in mineral levels toward the distal shaft. Increases in mineral density to higher fra...
American journal of physiology. Regulatory, integrative and comparative physiology, 2001
We previously showed that psychological stressors alter plasma levels of osteocalcin (pOC), a bon... more We previously showed that psychological stressors alter plasma levels of osteocalcin (pOC), a bone-specific mineral binding protein, in ways that differ with the type of stressor. To determine effects of chronic stress, we examined vertebrae, pOC, and corticosterone levels from conscious rats subjected to foot-restraint immobilization (Immo) daily for 1-42 times. After 40-42 Immo, basal pOC was decreased by 25% compared with unstressed rats, and the subsequent rise in pOC during Immo was blunted. Corticosterone was elevated 10-fold during Immo. Immo for seven times did not change vertebral OC concentration, but caused a slight decrease in calcium and phosphorous concentrations in younger rats. Rats Immo for 42 times exhibited reduced body weight, vertebral weight, and vertebral OC concentration but no significant differences in vertebral mineral concentrations. Body fat content was visibly decreased. We do not know the source of or the stimulus for the initial rise in pOC. We conclu...