Type H blood vessels in bone modeling and remodeling

Peng, Yi; Wu, Song; Li, Yusheng; Crane, Janet L.

doi:10.7150/thno.34126

Cited by 325 publications

(264 citation statements)

References 95 publications

(114 reference statements)

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“…During bone modeling and remodeling, endocrine and paracrine factors induce migration and differentiation of progenitor cells to couple angiogenesis and osteogenesis . POCs have emerged as an important paracrine source of both angiogenic and osteogenic coupling factors.…”

Section: Discussionmentioning

confidence: 59%

Glucocorticoids Disrupt Skeletal Angiogenesis Through Transrepression of NF-κB–Mediated Preosteoclast Pdgfb Transcription in Young Mice

Peng

et al. 2020

Journal of Bone and Mineral Research

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In the growing skeleton, angiogenesis is intimately coupled with osteogenesis. Chronic, high doses of glucocorticoids (GCs) are associated with decreased bone vasculature and induce osteoporosis and growth failure. The mechanism of GC‐suppression of angiogenesis and relationship to osteoporosis and growth retardation remains largely unknown. Type H vessels, which are regulated by preosteoclast (POC) platelet‐derived growth factor–BB (PDGF‐BB), are specifically coupled with bone formation and development. We determined the effect of GCs on POC synthesis of PDGF‐BB in relation to type H vessel formation, bone mass, and bone growth in the distal femur of 2‐week‐old young mice receiving prednisolone or vehicle for 2, 4, or 6 weeks. After 2 weeks of prednisolone, the number of POCs were unchanged while POC synthesis of PDGF‐BB was reduced. Longer treatment with prednisolone reduced POCs numbers and PDGF‐BB. These changes were associated with a reduction in type H vessels, bone formation rate, bone mass, and bone length at each time point. In vitro, excessive concentrations of prednisolone (10−6M) resulted in decreased PDGF‐BB concentration and POC numbers. Conditioned medium from POC cultures treated with control concentration of prednisolone (10−7M) or recombinant PDGF‐BB stimulated endothelial tube formation, whereas conditioned medium from control concentration of prednisolone‐treated POC cultures neutralized by PDGF‐BB antibody or excessive prednisolone inhibited endothelial tube formation. Administration of excessive prednisolone attenuated the P65 subunit of nuclear factor kappa B (NF‐κB) binding to the Pdgfb promoter, resulting in lower Pdgfb transcription. Co‐treatment with excessive prednisolone and the glucocorticoid receptor (GR) antagonist (RU486), GR siRNA, or TNFα rescued NF‐κB binding to the Pdgfb promoter and endothelial tube formation. These results indicate that PDGF‐BB synthesis in POCs is suppressed by GCs through transrepression of GR/NF‐κB, thus inhibiting type H vessel formation and associated osteoporosis and growth failure. © 2020 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 59%

Glucocorticoids Disrupt Skeletal Angiogenesis Through Transrepression of NF-κB–Mediated Preosteoclast Pdgfb Transcription in Young Mice

Peng

et al. 2020

Journal of Bone and Mineral Research

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“…Recently, the blood vessel formation process was identified as two stages [48][49][50]. The first stage is vasculogenesis, when mesodermal precursor cells undergo angioblasts differentiation toward ECs.…”

Section: Discussionmentioning

confidence: 99%

“…Since blood vessels carry oxygen and nutrients to all cells and remove waste products from tissues, angiogenesis is a prerequisite for osteogenesis [27,49,50,63]. It is accepted that osteogenesis and angiogenesis are coupled during the bone development [27,29].…”

Section: Discussionmentioning

confidence: 99%

BMP9 exhibits dual and coupled roles in inducing osteogenic and angiogenic differentiation of mesenchymal stem cells

Xiao

Wang

et al. 2020

Bioscience Reports

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Bone morphogenetic protein (BMP) 9 (BMP9) is one of most potent BMPs in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Recently, evidence has shown that osteogenesis and angiogenesis are coupled, however, it is unclear whether BMP9 induces MSC differentiation into endothelial-like cells and further promotes blood vessel formation. In the present study, we explored the potential of BMP9-induced angiogenic differentiation of MSCs, and the relationship between BMP9-induced osteogenic and angiogenic differentiation of MSCs. Osteogenic activities and angiogenic differentiation markers were analyzed at mRNA and protein levels. In vivo osteogenic and angiogenic differentiation of MSCs were tested by the ectopic bone formation model. We identified that adenoviral vectors effectively transduced in immortalized mouse embryonic fibroblasts (iMEFs) and expressed BMP9 with high efficiency. We found that BMP9 induces early and late osteogenic differentiation, and it up-regulated osteogenic marker expression in MSCs. Meanwhile, BMP9 induces angiogenic differentiation of MSCs via the expression of vascular endothelial growth factor a (VEGFa) and CD31 at both mRNA and protein levels. CD31-positive cells were also increased with the stimulation of BMP9. The ectopic bone formation tests found that BMP9-induced trabecular bone formation was coupled with the expression of blood vessel formation markers and sinusoid capillary formation. These findings suggest that BMP9 exhibits dual and coupled roles in inducing osteogenic and angiogenic differentiation of MSCs.

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“…(75) VEGFA exists in multiple isoforms-VEGF 120 , VEGF 164 , and VEGF 188 in mouse and VEGF 121 , VEGF 145 , VEGF 165 , VEGF 183 , VEGF 186 , VEGF 189 , and VEGF 206 in human, which elicit diverse biological processes. (76,77) Nevertheless, reduced endochondral angiogenesis and mineralization occurs in mice expressing only VEGF 120 isoform. (78) Mice with a combined loss of VEGF 164 and VEGF 188 demonstrate reduced angiogenesis, perturbed vessel invasion into hypertrophic chondrocytes, impaired bone formation and shortened limbs.…”

Section: Role Of Vegfa During Bone Developmentmentioning

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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Type H blood vessels in bone modeling and remodeling

Cited by 325 publications

References 95 publications

Glucocorticoids Disrupt Skeletal Angiogenesis Through Transrepression of NF-κB–Mediated Preosteoclast Pdgfb Transcription in Young Mice

Glucocorticoids Disrupt Skeletal Angiogenesis Through Transrepression of NF-κB–Mediated Preosteoclast Pdgfb Transcription in Young Mice

BMP9 exhibits dual and coupled roles in inducing osteogenic and angiogenic differentiation of mesenchymal stem cells

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

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