Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity

Lane, Nancy E.; Mohan, Geetha; Yao, Wei; Shidara, Kie; Lay, Yu-An E.; Jia, Junjing; Dubrovsky, Alanna; Kimmel, Donald B.

doi:10.1016/j.bonr.2018.10.003

Cited by 10 publications

(11 citation statements)

References 48 publications

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“…In a glucocorticoid-treated mouse model that yields an osteonecrosis prevalence of 36%, CD31 and endomucin positive cells declined in glucocorticoid treated mice relative to vehicle. However, while treatment with LLP2A-Alendronate (a bone targeted agent that guides endogenous or exogenous mesenchymal stromal cells to bone) or parathyroid hormone (PTH) increased CD31 and endomucin cells similar to vehicle group, no change in prevalence of osteonecrosis was noted 86. Using different rodent models of osteonecrosis and PTH, other studies have reported an improvement in prevalence of osteonecrosis with a combination treatment of core decompression and PTH, including improvement in neovascularization 87.…”

Section: Type H Vessels In Bone Disordersmentioning

confidence: 99%

Type H blood vessels in bone modeling and remodeling

et al. 2020

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In the mammalian skeletal system, osteogenesis and angiogenesis are intimately linked during bone growth and regeneration in bone modeling and during bone homeostasis in bone remodeling. Recent studies have expanded our knowledge about the molecular and cellular mechanisms responsible for coupling angiogenesis and bone formation. Type H vessels, termed such because of high expression of Endomucin (Emcn) and CD31, have recently been identified and have the ability to induce bone formation. Factors including platelet-derived growth factor type BB (PDGF-BB), slit guidance ligand 3 (SLIT3), hypoxia-inducible factor 1-alpha (HIF-1α), Notch, and vascular endothelial growth factor (VEGF) are involved in the coupling of angiogenesis and osteogenesis. This review summarizes the current understanding of signaling pathways that regulate type H vessels and how type H vessels modulate osteogenesis. Further studies dissecting the regulation and function of type H vessels will provide new insights into the role of bone vasculature in the metabolism of the skeleton. We also discuss considerations for therapeutic approaches targeting type H vessels to promote fracture healing, prevent pathological bone loss, osteonecrosis, osteoarthritis, and bone metastases.

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Section: Type H Vessels In Bone Disordersmentioning

confidence: 99%

Type H blood vessels in bone modeling and remodeling

et al. 2020

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“…( 161,162 ) Type H ECs decline in glucocorticoid‐treated mice compared with the vehicle group. ( 163 ) Further, a combination treatment of core decompression and parathyroid hormone (PTH) has been used to promote neo‐angiogenesis and bone repair, decreasing the prevalence of osteonecrosis in mouse models. Nevertheless, further research is required to investigate the benefit of blood vessel targeted therapy under clinical settings of osteonecrosis in humans.…”

Section: Osteonecrosismentioning

confidence: 99%

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

Chen

Hendriks

Chatzis

et al. 2020

Journal of Bone and Mineral Research

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Bone vasculature and bone marrow vascular niches supply oxygen, nutrients, and secrete angiocrine factors required for the survival, maintenance, and self-renewal of stem and progenitor cells. In the skeletal system, vasculature creates nurturing niches for bone and blood-forming stem cells. Blood vessels regulate hematopoiesis and drive bone formation during development, repair, and regeneration. Dysfunctional vascular niches induce skeletal aging, bone diseases, and hematological disorders. Recent cellular and molecular characterization of the bone marrow microenvironment has provided unprecedented insights into the complexity, heterogeneity, and functions of the bone vasculature and vascular niches. The bone vasculature is composed of distinct vessel subtypes that differentially regulate osteogenesis, hematopoiesis, and disease conditions in bones. Further, bone marrow vascular niches supporting stem cells are often complex microenvironments involving multiple different cell populations and vessel subtypes. This review provides an overview of the emerging vascular cell heterogeneity in bone and the new roles of the bone vasculature and associated vascular niches in health and disease.

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“…More importantly, we found that the development of ON was independent of bone mass. Specifically, a potent bone anabolic agent, such as PTH, activated osteoblast activity, and increased bone mass but failed to reduce the incidence of ON 30 …”

Section: Discussionmentioning

confidence: 99%

An MSC bone‐homing compound, Rab001, increases bone mass and reduces the incidence of osteonecrosis in a glucocorticoid‐induced osteonecrosis mouse model

Jiang

Liu

Xiang³

et al. 2020

Clin Exp Pharma Physio

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Currently, there are no effective medications to either prevent or slow the progression of atraumatic osteonecrosis (ON). The objective of this study is to determine the effects of bone‐targeted delivery of mesenchymal stem cells on the prevalence of ON in a glucocorticoid (GC)‐induced mouse model. Eight‐week‐old male BALB/c mice were randomized into groups that received placebo (PL), prednisolone (GC), or concurrent treatments with GC + mesenchymal stromal cells (MSCs), Rab001 or GC + Rab001 + MSCs. Human parathyroid hormone (hPTH) was used as a positive control for bone anabolism. Mice were killed after 30 days, and quantitative measurements of bone mass, bone strength, prevalent ON at the distal femoral epiphysis (DFE) were performed. Angiogenesis was accessed by RNA‐Seq, the circulating angiogenic markers, as well as by immunohistochemical staining. We have showed that a novel agent, Rab001 that can noncovalently bind to mesenchymal stem cells (MSC) and direct them to the bone, prevents the incidence of glucocorticoid‐induced osteonecrosis in the mouse. In contrast, PTH, a bone anabolic treatment, preserves bone mass but sustains higher ON incidence than Rab001+/− MSC‐treated mice. The results of these experiments reveal that glucocorticoids increase the prevalence of ON, and agents that prevent loss of bone vascularity appear to prevent the development of ON. This intervention might be useful in patients with early stages of atraumatic ON.

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Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity

Cited by 10 publications

References 48 publications

Type H blood vessels in bone modeling and remodeling

Type H blood vessels in bone modeling and remodeling

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

An MSC bone‐homing compound, Rab001, increases bone mass and reduces the incidence of osteonecrosis in a glucocorticoid‐induced osteonecrosis mouse model

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