Splenomegaly, myeloid lineage expansion and increased osteoclastogenesis in osteogenesis imperfecta murine

Matthews, Brya G.; Roeder, E.; Wang, Xi; Aguila, Héctor L.; Lee, Sun-Kyeong; Grčević, Danka; Kalajzić, Ivo

doi:10.1016/j.bone.2017.06.004

Cited by 20 publications

(10 citation statements)

References 46 publications

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“…Notably, the analysis of circulating markers of bone turnover in the serum showed greatly increased levels of CTX-I in oim/oim (consistent with previous findings from others ( Matthews et al, 2017 )) and oim-RANKL-cKO mice compared to WT and RANKL-cKO. However, no overall significant changes in TRAcP5b activity were detected among the four genotypes.…”

Section: Discussionsupporting

confidence: 90%

Loss of RANKL in osteocytes dramatically increases cancellous bone mass in the osteogenesis imperfecta mouse (oim)

et al. 2018

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Osteogenesis imperfecta (OI) is characterized by osteopenia and bone fragility, and OI patients during growth often exhibit high bone turnover with the net result of low bone mass. Recent evidence shows that osteocytes significantly affect bone remodeling under physiological and pathological conditions through production of osteoclastogenic cytokines. The receptor activator of nuclear factor kappa-B ligand (RANKL) produced by osteocytes for example, is a critical mediator of bone loss caused by ovariectomy, low-calcium diet, unloading and glucocorticoid treatment. Because OI bone has increased density of osteocytes and these cells are embedded in matrix with abnormal type I collagen, we hypothesized that osteocyte-derived RANKL contributes to the OI bone phenotype. In this study, the conditional loss of RANKL in osteocytes in oim/oim mice (oim-RANKL-cKO) resulted in dramatically increased cancellous bone mass in both the femur and lumbar spine compared to oim/oim mice. Bone cortical thickness increased significantly only in spine but ultimate bone strength in the long bone and spine was minimally improved in oim-RANKL-cKO mice compared to oim/oim mice. Furthermore, unlike previous findings, we report that oim/oim mice do not exhibit high bone turnover suggesting that their low bone mass is likely due to defective bone formation and not increased bone resorption. The loss of osteocyte-derived RANKL further diminished parameters of formation in oim-RANKL-cKO. Our results indicate that osteocytes contribute significantly to the low bone mass observed in OI and the effect of loss of RANKL from these cells is similar to its systemic inhibition.

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Section: Discussionsupporting

confidence: 90%

Loss of RANKL in osteocytes dramatically increases cancellous bone mass in the osteogenesis imperfecta mouse (oim)

et al. 2018

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“…In most cases, 2-3 animals of the same sex were pooled to generate a sample. Briefly, after removal of muscle tissue, bone marrow was flushed and underwent red blood cell lysis (71). Periosteum was scraped off the bone surface and digested in PBS containing 0.05% Collagenase P and 0.2% hyaluronidase (Sigma Aldrich, St Louis, MO, USA) for 1h at 37°C.…”

Section: Cell Isolationmentioning

confidence: 99%

Heterogeneity of murine periosteum progenitors involved in fracture healing

Matthews

Novak

Sbrana

et al. 2021

eLife

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The periosteum is the major source of cells involved in fracture healing. We sought to characterize progenitor cells and their contribution to bone fracture healing. The periosteum is highly enriched for progenitor cells, including Sca1+ cells, CFU-F and label-retaining cells compared to the endosteum and bone marrow. Using lineage tracing, we demonstrate that αSMA identifies long-term, slow-cycling, self-renewing osteochondroprogenitors in the adult periosteum that are functionally important for bone formation during fracture healing. In addition, Col2.3CreER-labeled osteoblast cells contribute around 10% of osteoblasts, but no chondrocytes in fracture calluses. Most periosteal osteochondroprogenitors following fracture, can be targeted by αSMACreER. Previously identified skeletal stem cell populations were common in periosteum, but contained high proportions of mature osteoblasts. We have demonstrated that the periosteum is highly enriched for skeletal progenitor cells and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing.

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“…In most cases, 2-3 animals of the same sex were pooled to generate a sample. Briefly, after removal of muscle tissue, bone marrow was flushed and underwent red blood cell lysis (57). Periosteum was scraped off the bone surface and digested in PBS containing 0.05% Collagenase P (Roche, IN, USA) and 0.2% hyaluronidase (Sigma Aldrich, St Louis, MO, USA) for 1h at 37°C.…”

Section: Cell Isolationmentioning

confidence: 99%

Heterogeneity of murine periosteum progenitors involved in fracture healing

Matthews

Novak

Sbrana

et al. 2020

Preprint

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The periosteum is the major source of cells involved in fracture healing. We sought to characterize differences in progenitor cell populations between periosteum and other bone compartments, and identify periosteal cells involved in fracture healing. The periosteum is highly enriched for progenitor cells, including Sca1+ cells, CFU-F and label-retaining cells. Lineage tracing with αSMACreER identifies periosteal cells that contribute to >80% of osteoblasts and ~40% of chondrocytes following fracture.A subset of αSMA+ cells are quiescent long-term injury-responsive progenitors. Ablation of αSMA+ cells impairs fracture callus formation. In addition, committed osteoblast-lineage cells contributed around 10% of osteoblasts, but no chondrocytes in fracture calluses. Most periosteal progenitors, particularly those that form osteoblasts, can be targeted by αSMACreER. We have demonstrated that the periosteum is highly enriched for skeletal stem and progenitor cells and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing.

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Splenomegaly, myeloid lineage expansion and increased osteoclastogenesis in osteogenesis imperfecta murine

Cited by 20 publications

References 46 publications

Loss of RANKL in osteocytes dramatically increases cancellous bone mass in the osteogenesis imperfecta mouse (oim)

Loss of RANKL in osteocytes dramatically increases cancellous bone mass in the osteogenesis imperfecta mouse (oim)

Heterogeneity of murine periosteum progenitors involved in fracture healing

Heterogeneity of murine periosteum progenitors involved in fracture healing

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