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Papers by Alexandra Roland

Research paper thumbnail of Dietary saturated fatty acid palmitate promotes cartilage lesions and activates the unfolded protein response pathway in mouse knee joints

PLOS ONE

Increased intake of dietary saturated fatty acids has been linked to obesity and the development ... more Increased intake of dietary saturated fatty acids has been linked to obesity and the development of Osteoarthritis (OA). However, the mechanism by which these fats promote cartilage degradation and the development of OA is not clearly understood. Here, we report the effects of consumption of common dietary saturated and unsaturated fatty acids, palmitate and oleate, respectively, on body weight, metabolic factors, and knee articular cartilage in a mouse model of diet-induced obesity. Mice fed on a diet rich in saturated or unsaturated fatty acid gained an equal amount of weight; however, mice fed a palmitate diet, but not a control or oleate diet, exhibited more cartilage lesions and increased expression of 1) unfolded protein response (UPR)/endoplasmic reticulum (ER) stress markers including BIP, P-IRE1α, XBP1, ATF4, and CHOP; 2) apoptosis markers CC3 and C-PARP; and 3) negative cell survival regulators Nupr1 and TRB3, in knee articular cartilage. Palmitate-induced apoptosis was co...

Research paper thumbnail of Naturally occurring osteochondrosis latens lesions identified by quantitative and morphological 10.5 T MRI in pigs

Journal of Orthopaedic Research

Research paper thumbnail of Quantitative T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in an in vivo piglet model of Legg-Calvé-Perthes disease

Osteoarthritis and Cartilage

Research paper thumbnail of Overexpression of Peroxiredoxin 3 in Cartilage Reduces the Severity of Age‐Related Osteoarthritis But Not Surgically Induced Osteoarthritis in Mice

ACR Open Rheumatology

Objective. The study objective was to determine whether overexpression of the mitochondrial antio... more Objective. The study objective was to determine whether overexpression of the mitochondrial antioxidant peroxidase, peroxiredoxin 3 (Prx3), reduces the severity of osteoarthritis (OA) in mice. Methods. Age-related OA (age 18 and 24 months) and OA induced by destabilization of the medial meniscus (DMM at age 6 months) were assessed in male mice that overexpress a human Prdx3 transgene encoding the Prx3 protein. Lox-stop-lox-Prdx3 (iPrdx3) mice were crossed with aggrecan-Cre ERT2 mice to produce iPrdx3AgCre ERT2 or with Col2Cre to produce iPrdx3Col2Cre mice. Germline transgenics (Prdx3Tg) were also evaluated. Prx3 protein level was assessed by immunoblotting and functionally after induction of elevated mitochondrial hydrogen peroxide (H 2 O 2) using menadione. Histological sections of stifle joints were scored for cartilage damage (Articular Cartilage Structure score [ACS]), osteophytes, and synovial hyperplasia and were evaluated by histomorphometry. Results. Overexpression of Prx3 maintained mitochondrial membrane integrity and inhibited p38 phosphorylation in the presence of elevated H 2 O 2. ACS scores of 18-month-old iPrdx3AgCre ERT2 mice (mean AE SD, 4.88 AE 5.05) were significantly lower than age-matched iPrdx3 controls (11.75 AE 6.34, P = 0.002) and trended lower in the 18-month Prdx3Tg group (P = 0.14), whereas no significant differences between experimental and control groups at 24 months of age or in OA induced by DMM surgery were noted. Osteophyte scores trended lower in the 18-month-old Prdx3Tg group (P = 0.09) and at 24 months in the iPrdx3Col2Cre mice (P = 0.05). There were no significant group differences in synovial hyperplasia or histomorphometric measures. Conclusion. Overexpression of the mitochondrial peroxidase Prx3 reduced the severity of age-related OA, but not at advanced ages and not in DMM-induced OA in younger mice.

Research paper thumbnail of Genetic deletion of nuclear protein-1 reduces the severity of cartilage lesions in a mouse model of post-traumatic osteoarthritis

Osteoarthritis and Cartilage, 2021

Research paper thumbnail of Optimization of histologic grading schemes in spontaneous and surgically-induced murine models of osteoarthritis

Osteoarthritis and Cartilage, 2021

Objective: To compare the Osteoarthritis Research Society International (OARSI) and Articular Car... more Objective: To compare the Osteoarthritis Research Society International (OARSI) and Articular Cartilage Structure (ACS) grading schemes applied to multiple and single sections, along with additional histologic measures, in two mouse models of Osteoarthritis (OA). Methods: Six coronal histologic stifle joint sections were collected from 40 C57BL/6J mice, including aged mice with spontaneous OA (approximately 18 months of age; n ¼ 15) and young (12-week-old) mice that either underwent destabilization of the medial meniscus (DMM) surgery (n ¼ 15) or sham surgery (n ¼ 10). Sections were evaluated with the standard OARSI (0e6) scheme, a modified OARSI scheme, the ACS (0e12) scheme, histomorphometry of cartilage and bone, and scoring of osteophytes (0e3) and synovial hyperplasia (0e3). Principal components analysis (PCA) was used to determine the features explaining the greatest variability among the sections. Results: The grading schemes performed similarly when applied to a single mid-coronal section or six total coronal sections per joint. OARSI grading produced similar results when applied to hematoxylin and eosin or toluidine blue-stained sections. Aged mice had higher severity scores in the LTP than DMM mice (mid-coronal OARSI grade aged ¼ 2.3 and DMM ¼ 1.1, p ¼ 0.0006; ACS grade aged ¼ 4.1 and DMM ¼ 1.6, p ¼ 0.0024). PCA resulted in retention of four factors that accounted for 78.4% of the total variance. Factor 1 (36.4%) included the OARSI grade, ACS grade, Toluidine blue grade, articular cartilage area and thickness and the osteophyte grade. Conclusions: Grading of a single mid-coronal section using either the OARSI or ACS schemes combined with osteophyte and histomorphometric measures can consistently define OA severity in mice.

Research paper thumbnail of Systemic versus free antibiotic delivery in preventing acute exogenous implant related infection in a rat model

Journal of Orthopaedic Research, 2021

We studied systemic ceftriaxone, and free/local tobramycin and doxycycline in a controlled rat mo... more We studied systemic ceftriaxone, and free/local tobramycin and doxycycline in a controlled rat model representing a generic acute exogenous joint infection. We hypothesized that evidence of infection (quantitative colony forming units [CFU], qualitative scanning electron microscopy [SEM], histopathology) (1a) would be reduced with local versus systemic antibiotic, (1b) any antibiotic would be superior to control, (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4‐week euthanasia. Study groups included infected and noninfected (1) control (no treatment), (2) systemic ceftriaxone (daily), (3) local tobramycin, and (4) local doxycycline (10 rats/group; power = 0.8). With IACUC approval, a reliable acute exogenous joint infection was created by slowly injecting 50‐μl, 104 CFU Staphylococcus aureus, into the distal femoral medullary canal. The antibiotic formulation was introduced locally to the femoral canal and joint space. After 4 weeks, serum, pin, bone, and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on the surface of the pin, histopathology identified tissue response, liquid chromatography/mass spectrometry quantified plasma antibiotic. (1) Groups receiving any antibiotic reported lower CFU/ml in synovium compared with no treatment. (2) In the synovium, free/local tobramycin reduced CFU/ml to a greater extent than free/local doxycycline (p < 0.05). (3) Antibiotic in plasma after the local application was nondetectable in all groups after 4 weeks. SEM revealed no difference in biofilm on pin among all groups.

Research paper thumbnail of T1ρ and T2 mapping detect acute ischemic injury in a piglet model of Legg–Calvé–Perthes disease

Journal of Orthopaedic Research, 2021

This study investigated the sensitivity of T1ρ and T2 relaxation time mapping to detect acute isc... more This study investigated the sensitivity of T1ρ and T2 relaxation time mapping to detect acute ischemic injury to the secondary ossification center (SOC) and epiphyseal cartilage of the femoral head in a piglet model of Legg–Calvé–Perthes disease. Six piglets underwent surgery to induce global right femoral head ischemia and were euthanized 48 h later. Fresh operated and contralateral‐control femoral heads were imaged ex vivo with T1, T2, and T1ρ mapping using a 9.4T magnetic resonance imaging scanner. The specimens were imaged a second time after a freeze/thaw cycle and then processed for histology. T1, T2, and T1ρ measurements in the SOC, epiphyseal cartilage, articular cartilage, and metaphysis were compared between operated and control femoral heads using paired t tests. The effects of freeze/thaw, T1ρ spin‐lock frequency, and fat saturation were also investigated. Five piglets with histologically confirmed ischemic injury were quantitatively analyzed. T1ρ was increased in the SOC (101 ± 15 vs. 73 ± 16 ms; p = 0.0026) and epiphyseal cartilage (84.9 ± 9.2 vs. 74.3 ± 3.6 ms; p = 0.031) of the operated versus control femoral heads. T2 was also increased in the SOC (28.7 ± 2.0 vs. 22.7 ± 1.7; p = 0.0037) and epiphyseal cartilage (57.4 ± 4.7 vs. 49.0 ± 2.7; p = 0.0041). No changes in T1 were detected. The sensitivities of T1ρ and T2 mapping in detecting ischemic injury were maintained after a freeze/thaw cycle, and T1ρ sensitivity was maintained after varying spin‐lock frequency and applying fat saturation. In conclusion, T1ρ and T2 mapping are sensitive in detecting ischemic injury to the SOC and epiphyseal cartilage of the femoral head as early as 48 h after ischemia induction.

Research paper thumbnail of Deletion of JNK Enhances Senescence in Joint Tissues and Increases the Severity of Age‐Related Osteoarthritis in Mice

Arthritis & Rheumatology, 2020

Objective.-Determine the role of c-Jun N-terminal kinase (JNK) signaling in the development of os... more Objective.-Determine the role of c-Jun N-terminal kinase (JNK) signaling in the development of osteoarthritis (OA) induced by joint injury and aging in mice. Methods.-Destabilization of the medial meniscus (DMM) or sham surgery was performed on 12 week-old mice and OA evaluated 8 weeks after surgery. Groups included wild type-controls, JNK1 −/− , JNK2 −/− , and JNK1 fl/fl JNK2 −/− aggecan-Cre ERT2 double knockouts. The aging study used wild-type controls, JNK1 −/− , and JNK2 −/− mice evaluated at 18 months of age. Knee joints were evaluated by scoring articular cartilage structure (ACS), toluidine blue staining, osteophytes, synovial hyperplasia, histomorphometry and immunostaining for the senescence marker p16 Ink4a. Production of MMP-13 in cartilage explants in response to fibronectin fragments was measured by ELISA. Results.-There were no differences after DMM surgery between wild-type and the JNK knockout groups in ACS, toluidine blue or osteophyte scores and no differences in MMP-13

Research paper thumbnail of Microenvironmental Influences on Articular Chondrocyte Differentiation

Orthopaedic Journal of Sports Medicine, 2020

Background: Immature articular cartilage (a.k.a. articular epiphyseal cartilage complex, AECC), s... more Background: Immature articular cartilage (a.k.a. articular epiphyseal cartilage complex, AECC), serves dual functions as an articulating layer and surface growth plate. The AECC originates from an uninterrupted cartilaginous template during embryogenesis, presumably stemming from the same pool of progenitors, but it is unclear how the articulating layer is maintained throughout life, while the surface growth plate undergoes endochondral ossification. Hypothesis: The function and fate of chondrocytes in the AECC are not predetermined in the embryo, but instead can be influenced during development by biochemical and/or biomechanical stimuli in the cellular microenvironment. Methods: Microenvironments of the articulating layer and surface growth plate were switched in an in vivo goat model. Twelve 3-week-old goats were used. Osteochondral autografts were harvested from medial and lateral condyles and trochlea of the distal femur. Subchondral bone was removed (Figures 1A and 1B). Grafts...

Research paper thumbnail of Clostridium difficile Enterocolitis in a Captive Geoffroy’s Spider Monkey (Ateles geoffroyi) and Common Marmosets (Callithrix jacchus)

Veterinary Pathology, 2019

Clostridium difficile is a well-documented cause of enterocolitis in several species, including h... more Clostridium difficile is a well-documented cause of enterocolitis in several species, including humans, with limited documentation in New World nonhuman primates. We report several cases of C. difficile–associated pseudomembranous enterocolitis, including a case in a Geoffroy’s spider monkey ( Ateles geoffroyi) and several cases in common marmosets ( Callithrix jacchus). The histologic lesions included a spectrum of severity, with most cases characterized by the classic “volcano” lesions described in humans and several other animal species. C. difficile was isolated from the colon of the spider monkey, while the presence of toxin A or toxin B or of the genes of toxin A or B by polymerase chain reaction served as corroborative evidence in several affected marmosets. C. difficile should be considered a cause of enterocolitis in these species.

Research paper thumbnail of The effect of vitamin K insufficiency on histological and structural properties of knee joints in aging mice

Osteoarthritis and Cartilage Open, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Pathology in Practice

Journal of the American Veterinary Medical Association, 2011

Research paper thumbnail of Dietary saturated fatty acid palmitate promotes cartilage lesions and activates the unfolded protein response pathway in mouse knee joints

PLOS ONE

Increased intake of dietary saturated fatty acids has been linked to obesity and the development ... more Increased intake of dietary saturated fatty acids has been linked to obesity and the development of Osteoarthritis (OA). However, the mechanism by which these fats promote cartilage degradation and the development of OA is not clearly understood. Here, we report the effects of consumption of common dietary saturated and unsaturated fatty acids, palmitate and oleate, respectively, on body weight, metabolic factors, and knee articular cartilage in a mouse model of diet-induced obesity. Mice fed on a diet rich in saturated or unsaturated fatty acid gained an equal amount of weight; however, mice fed a palmitate diet, but not a control or oleate diet, exhibited more cartilage lesions and increased expression of 1) unfolded protein response (UPR)/endoplasmic reticulum (ER) stress markers including BIP, P-IRE1α, XBP1, ATF4, and CHOP; 2) apoptosis markers CC3 and C-PARP; and 3) negative cell survival regulators Nupr1 and TRB3, in knee articular cartilage. Palmitate-induced apoptosis was co...

Research paper thumbnail of Naturally occurring osteochondrosis latens lesions identified by quantitative and morphological 10.5 T MRI in pigs

Journal of Orthopaedic Research

Research paper thumbnail of Quantitative T2 and T1ρ mapping are sensitive to ischemic injury to the epiphyseal cartilage in an in vivo piglet model of Legg-Calvé-Perthes disease

Osteoarthritis and Cartilage

Research paper thumbnail of Overexpression of Peroxiredoxin 3 in Cartilage Reduces the Severity of Age‐Related Osteoarthritis But Not Surgically Induced Osteoarthritis in Mice

ACR Open Rheumatology

Objective. The study objective was to determine whether overexpression of the mitochondrial antio... more Objective. The study objective was to determine whether overexpression of the mitochondrial antioxidant peroxidase, peroxiredoxin 3 (Prx3), reduces the severity of osteoarthritis (OA) in mice. Methods. Age-related OA (age 18 and 24 months) and OA induced by destabilization of the medial meniscus (DMM at age 6 months) were assessed in male mice that overexpress a human Prdx3 transgene encoding the Prx3 protein. Lox-stop-lox-Prdx3 (iPrdx3) mice were crossed with aggrecan-Cre ERT2 mice to produce iPrdx3AgCre ERT2 or with Col2Cre to produce iPrdx3Col2Cre mice. Germline transgenics (Prdx3Tg) were also evaluated. Prx3 protein level was assessed by immunoblotting and functionally after induction of elevated mitochondrial hydrogen peroxide (H 2 O 2) using menadione. Histological sections of stifle joints were scored for cartilage damage (Articular Cartilage Structure score [ACS]), osteophytes, and synovial hyperplasia and were evaluated by histomorphometry. Results. Overexpression of Prx3 maintained mitochondrial membrane integrity and inhibited p38 phosphorylation in the presence of elevated H 2 O 2. ACS scores of 18-month-old iPrdx3AgCre ERT2 mice (mean AE SD, 4.88 AE 5.05) were significantly lower than age-matched iPrdx3 controls (11.75 AE 6.34, P = 0.002) and trended lower in the 18-month Prdx3Tg group (P = 0.14), whereas no significant differences between experimental and control groups at 24 months of age or in OA induced by DMM surgery were noted. Osteophyte scores trended lower in the 18-month-old Prdx3Tg group (P = 0.09) and at 24 months in the iPrdx3Col2Cre mice (P = 0.05). There were no significant group differences in synovial hyperplasia or histomorphometric measures. Conclusion. Overexpression of the mitochondrial peroxidase Prx3 reduced the severity of age-related OA, but not at advanced ages and not in DMM-induced OA in younger mice.

Research paper thumbnail of Genetic deletion of nuclear protein-1 reduces the severity of cartilage lesions in a mouse model of post-traumatic osteoarthritis

Osteoarthritis and Cartilage, 2021

Research paper thumbnail of Optimization of histologic grading schemes in spontaneous and surgically-induced murine models of osteoarthritis

Osteoarthritis and Cartilage, 2021

Objective: To compare the Osteoarthritis Research Society International (OARSI) and Articular Car... more Objective: To compare the Osteoarthritis Research Society International (OARSI) and Articular Cartilage Structure (ACS) grading schemes applied to multiple and single sections, along with additional histologic measures, in two mouse models of Osteoarthritis (OA). Methods: Six coronal histologic stifle joint sections were collected from 40 C57BL/6J mice, including aged mice with spontaneous OA (approximately 18 months of age; n ¼ 15) and young (12-week-old) mice that either underwent destabilization of the medial meniscus (DMM) surgery (n ¼ 15) or sham surgery (n ¼ 10). Sections were evaluated with the standard OARSI (0e6) scheme, a modified OARSI scheme, the ACS (0e12) scheme, histomorphometry of cartilage and bone, and scoring of osteophytes (0e3) and synovial hyperplasia (0e3). Principal components analysis (PCA) was used to determine the features explaining the greatest variability among the sections. Results: The grading schemes performed similarly when applied to a single mid-coronal section or six total coronal sections per joint. OARSI grading produced similar results when applied to hematoxylin and eosin or toluidine blue-stained sections. Aged mice had higher severity scores in the LTP than DMM mice (mid-coronal OARSI grade aged ¼ 2.3 and DMM ¼ 1.1, p ¼ 0.0006; ACS grade aged ¼ 4.1 and DMM ¼ 1.6, p ¼ 0.0024). PCA resulted in retention of four factors that accounted for 78.4% of the total variance. Factor 1 (36.4%) included the OARSI grade, ACS grade, Toluidine blue grade, articular cartilage area and thickness and the osteophyte grade. Conclusions: Grading of a single mid-coronal section using either the OARSI or ACS schemes combined with osteophyte and histomorphometric measures can consistently define OA severity in mice.

Research paper thumbnail of Systemic versus free antibiotic delivery in preventing acute exogenous implant related infection in a rat model

Journal of Orthopaedic Research, 2021

We studied systemic ceftriaxone, and free/local tobramycin and doxycycline in a controlled rat mo... more We studied systemic ceftriaxone, and free/local tobramycin and doxycycline in a controlled rat model representing a generic acute exogenous joint infection. We hypothesized that evidence of infection (quantitative colony forming units [CFU], qualitative scanning electron microscopy [SEM], histopathology) (1a) would be reduced with local versus systemic antibiotic, (1b) any antibiotic would be superior to control, (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4‐week euthanasia. Study groups included infected and noninfected (1) control (no treatment), (2) systemic ceftriaxone (daily), (3) local tobramycin, and (4) local doxycycline (10 rats/group; power = 0.8). With IACUC approval, a reliable acute exogenous joint infection was created by slowly injecting 50‐μl, 104 CFU Staphylococcus aureus, into the distal femoral medullary canal. The antibiotic formulation was introduced locally to the femoral canal and joint space. After 4 weeks, serum, pin, bone, and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on the surface of the pin, histopathology identified tissue response, liquid chromatography/mass spectrometry quantified plasma antibiotic. (1) Groups receiving any antibiotic reported lower CFU/ml in synovium compared with no treatment. (2) In the synovium, free/local tobramycin reduced CFU/ml to a greater extent than free/local doxycycline (p < 0.05). (3) Antibiotic in plasma after the local application was nondetectable in all groups after 4 weeks. SEM revealed no difference in biofilm on pin among all groups.

Research paper thumbnail of T1ρ and T2 mapping detect acute ischemic injury in a piglet model of Legg–Calvé–Perthes disease

Journal of Orthopaedic Research, 2021

This study investigated the sensitivity of T1ρ and T2 relaxation time mapping to detect acute isc... more This study investigated the sensitivity of T1ρ and T2 relaxation time mapping to detect acute ischemic injury to the secondary ossification center (SOC) and epiphyseal cartilage of the femoral head in a piglet model of Legg–Calvé–Perthes disease. Six piglets underwent surgery to induce global right femoral head ischemia and were euthanized 48 h later. Fresh operated and contralateral‐control femoral heads were imaged ex vivo with T1, T2, and T1ρ mapping using a 9.4T magnetic resonance imaging scanner. The specimens were imaged a second time after a freeze/thaw cycle and then processed for histology. T1, T2, and T1ρ measurements in the SOC, epiphyseal cartilage, articular cartilage, and metaphysis were compared between operated and control femoral heads using paired t tests. The effects of freeze/thaw, T1ρ spin‐lock frequency, and fat saturation were also investigated. Five piglets with histologically confirmed ischemic injury were quantitatively analyzed. T1ρ was increased in the SOC (101 ± 15 vs. 73 ± 16 ms; p = 0.0026) and epiphyseal cartilage (84.9 ± 9.2 vs. 74.3 ± 3.6 ms; p = 0.031) of the operated versus control femoral heads. T2 was also increased in the SOC (28.7 ± 2.0 vs. 22.7 ± 1.7; p = 0.0037) and epiphyseal cartilage (57.4 ± 4.7 vs. 49.0 ± 2.7; p = 0.0041). No changes in T1 were detected. The sensitivities of T1ρ and T2 mapping in detecting ischemic injury were maintained after a freeze/thaw cycle, and T1ρ sensitivity was maintained after varying spin‐lock frequency and applying fat saturation. In conclusion, T1ρ and T2 mapping are sensitive in detecting ischemic injury to the SOC and epiphyseal cartilage of the femoral head as early as 48 h after ischemia induction.

Research paper thumbnail of Deletion of JNK Enhances Senescence in Joint Tissues and Increases the Severity of Age‐Related Osteoarthritis in Mice

Arthritis & Rheumatology, 2020

Objective.-Determine the role of c-Jun N-terminal kinase (JNK) signaling in the development of os... more Objective.-Determine the role of c-Jun N-terminal kinase (JNK) signaling in the development of osteoarthritis (OA) induced by joint injury and aging in mice. Methods.-Destabilization of the medial meniscus (DMM) or sham surgery was performed on 12 week-old mice and OA evaluated 8 weeks after surgery. Groups included wild type-controls, JNK1 −/− , JNK2 −/− , and JNK1 fl/fl JNK2 −/− aggecan-Cre ERT2 double knockouts. The aging study used wild-type controls, JNK1 −/− , and JNK2 −/− mice evaluated at 18 months of age. Knee joints were evaluated by scoring articular cartilage structure (ACS), toluidine blue staining, osteophytes, synovial hyperplasia, histomorphometry and immunostaining for the senescence marker p16 Ink4a. Production of MMP-13 in cartilage explants in response to fibronectin fragments was measured by ELISA. Results.-There were no differences after DMM surgery between wild-type and the JNK knockout groups in ACS, toluidine blue or osteophyte scores and no differences in MMP-13

Research paper thumbnail of Microenvironmental Influences on Articular Chondrocyte Differentiation

Orthopaedic Journal of Sports Medicine, 2020

Background: Immature articular cartilage (a.k.a. articular epiphyseal cartilage complex, AECC), s... more Background: Immature articular cartilage (a.k.a. articular epiphyseal cartilage complex, AECC), serves dual functions as an articulating layer and surface growth plate. The AECC originates from an uninterrupted cartilaginous template during embryogenesis, presumably stemming from the same pool of progenitors, but it is unclear how the articulating layer is maintained throughout life, while the surface growth plate undergoes endochondral ossification. Hypothesis: The function and fate of chondrocytes in the AECC are not predetermined in the embryo, but instead can be influenced during development by biochemical and/or biomechanical stimuli in the cellular microenvironment. Methods: Microenvironments of the articulating layer and surface growth plate were switched in an in vivo goat model. Twelve 3-week-old goats were used. Osteochondral autografts were harvested from medial and lateral condyles and trochlea of the distal femur. Subchondral bone was removed (Figures 1A and 1B). Grafts...

Research paper thumbnail of Clostridium difficile Enterocolitis in a Captive Geoffroy’s Spider Monkey (Ateles geoffroyi) and Common Marmosets (Callithrix jacchus)

Veterinary Pathology, 2019

Clostridium difficile is a well-documented cause of enterocolitis in several species, including h... more Clostridium difficile is a well-documented cause of enterocolitis in several species, including humans, with limited documentation in New World nonhuman primates. We report several cases of C. difficile–associated pseudomembranous enterocolitis, including a case in a Geoffroy’s spider monkey ( Ateles geoffroyi) and several cases in common marmosets ( Callithrix jacchus). The histologic lesions included a spectrum of severity, with most cases characterized by the classic “volcano” lesions described in humans and several other animal species. C. difficile was isolated from the colon of the spider monkey, while the presence of toxin A or toxin B or of the genes of toxin A or B by polymerase chain reaction served as corroborative evidence in several affected marmosets. C. difficile should be considered a cause of enterocolitis in these species.

Research paper thumbnail of The effect of vitamin K insufficiency on histological and structural properties of knee joints in aging mice

Osteoarthritis and Cartilage Open, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Pathology in Practice

Journal of the American Veterinary Medical Association, 2011