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Papers by Norbert Laroche

Matrix Biology, May 1, 2016

Bone reports, May 1, 2022

Bone reports, Dec 1, 2022

Bone reports, May 1, 2022

HAL (Le Centre pour la Communication Scientifique Directe), Mar 23, 2017

Objective: By providing a weightlessness environment, spaceflight induces site-specific bone loss... more Objective: By providing a weightlessness environment, spaceflight induces site-specific bone loss in both human and mice but cellular mechanisms remains unclear. On the other hand, during aging, osteocyte apoptosis associated with lacunae mineral occlusions occurs and bone marrow fat increases. Here, we wanted to analyze the effects of spaceflight on osteocytes lacunae, osteocytes survival and marrow adiposity. Then, we aimed to investigate the events occurring after a short term of earth recovery.Material and Methods: Mature C57/Bl6 male mice flew on the 30-day space Russian BION-M1 high-orbit satellite mission. The Flight group was killed after landing, and the recovery group 8 days later. The ground control group was kept under spacecraft housing conditions. Osteocytes Lacunae of femur cortical sections were imaged using Synchrotron Radiation μCT (resolution 0.7 μm) and 3D shape descriptors were calculated and analysed. Medial, anterior, posterior and lateral zones were analyzed, each containing more than 1200 lacunae. Osteocytes death and bone marrow fat were investigated in femur by histology.Results: The lacunar volume fraction was significantly decreased in the Flight vs. Habitat Control group in medial zone(-33% and -38%, respectively; p<0.025). In the posterior zone, the length/width ratio was significantly decreased in the Flight vs. Habitat Control group, indicating a more spherical lacuna shape in the Flight group. Moreover, particularly in the posterior zone, the lacuna mean volume was significantly decreased and the fraction of smaller lacunae (less than 200μm3) was greater in Flight and Flight+Rec groups vs. Habitat Control. Furthermore, the ratio of empty overall lacunae was dramatically increased in Flight vs. Habitat Control group (11.44% vs. 3.64%, p<0.005) and remained elevated in the Flight+Rec group (9.71%, NS vs. Flight). Finally, femur bone marrow analyses revealed a marrow adipocytes invasion in Flight and Flight+Rec groups.Conclusion: We provide first evidences that one-month spaceflight induces osteocyte death along with decreased osteocyte lacunar volume and increases bone marrow fat, both being hallmarks of aging. No recovery was seen 8-day after landing. Given the critical role of osteocytes to orchestrate bone remodeling, their compromised survival might jeopardize bone reversibility, mainly in the most aged.

Scientific Reports, Oct 12, 2017

Conference proceedings, Aug 1, 2007

Bone micro-cracks receive an increasing attention to explain bone quality. They have mainly been ... more Bone micro-cracks receive an increasing attention to explain bone quality. They have mainly been observed in 2D with microscopic techniques. In this paper, we propose a method based on 3D Synchrotron Radiation micro-CT to analyze micro-cracks in human trabecular bone samples. Samples were imaged with a voxel size of 1.4 microm. Despite micro-cracks are visible, their automatic detection is challenging because of noise, artifacts, low-contrast, and partial volume effect. We propose a two-steps procedure, based on image enhancement and segmentation to address this problem. The method enables to get the 3D morphology of micro-cracks, shown for the first time with this precision. Future work will be devoted to extract quantitative parameters on the crack morphology.

PLOS ONE

Insights into the effects of osteoarthritis (OA) and physical interventions on the musculoskeleta... more Insights into the effects of osteoarthritis (OA) and physical interventions on the musculoskeletal system are limited. Our goal was to analyze musculoskeletal changes in OA mice and test the efficacy of 8-week exposure to hypergravity, as a replacement of physical activity. 16-week-old male (C57BL/6J) mice allocated to sham control and OA groups not centrifuged (Ctrl 1g and OA 1g, respectively) or centrifuged at 2g acceleration (Ctrl 2g and OA 2g). OA 1g displayed decreased trabecular bone in the proximal tibia metaphysis and increased osteoclastic activity and local TNFα gene expression, all entirely prevented by 2g gravitational therapy. However, while cortical bone of tibia midshaft was preserved in OA 1g (vs. ctrl), it is thinner in OA 2g (vs. OA 1g). In the hind limb, OA at 1g increased fibers with lipid droplets by 48% in the tibialis anterior, a fact fully prevented by 2g. In Ctrl, 2g increased soleus, tibialis anterior and gastrocnemius masses. In the soleus of both Ctrl and...

μCT scout images of whole femurs (E), and femur length (F) at 4 and 12 mo of age for WT () and mu... more μCT scout images of whole femurs (E), and femur length (F) at 4 and 12 mo of age for WT () and mutant () female mice; similar results were obtained with males (not depicted). Two-dimensional images of midshaft sections in specimens from both genotypes (G) and cortical thickness (H) at 4 and 12 mo of age for and male and female mice. Values are the mean ± the SEM of 6–10 samples. **, P < 0.01; ****, P < 0.0001 versus matched WT; #, P < 0.05 versus matched females.<b>Copyright information:</b>Taken from "Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis"The Journal of Experimental Medicine 2008;205(5):1145-1153.Published online 12 May 2008PMCID:PMC2373846.

Frontiers in Immunology, 2021

Sjögren’s syndrome (SjS) is a frequent systemic autoimmune disease responsible for a major decrea... more Sjögren’s syndrome (SjS) is a frequent systemic autoimmune disease responsible for a major decrease in patients’ quality of life, potentially leading to life-threatening conditions while facing an unmet therapeutic need. Hence, we assessed the immunogenicity, efficacy, and tolerance of IFN-Kinoid (IFN-K), an anti-IFNα vaccination strategy, in a well-known mouse model of systemic autoimmunity with SjS-like features: MRL/MpJ-Faslpr/lpr (MRL/lpr) mice. Two cohorts (with ISA51 or SWE01 as adjuvants) of 26 female MRL/lpr were divided in parallel groups, “controls” (not treated, PBS and Keyhole Limpet Hemocyanin [KLH] groups) or “IFN-K” and followed up for 122 days. Eight-week-old mice received intra-muscular injections (days 0, 7, 28, 56 and 84) of PBS, KLH or IFN-K, emulsified in the appropriate adjuvant, and blood samples were serially collected. At sacrifice, surviving mice were euthanized and their organs were harvested for histopathological analysis (focus score in salivary/lacrimal...

Calcified Tissue International, 2020

Scientific Reports, 2018

Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovi... more Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss. Active osteoclastic surfaces were increased from day 8 with RANKL upregulation. More surprisingly SOST and DKK1 were overexpressed from day 6 and followed by a dramatic decrease in bone formation from day 8. At the time of arthritis onset, SOST and DKK1 returned to control...