Angiogenesis stimulated by elevated PDGF-BB in subchondral bone contributes to osteoarthritis development

Su, Weiping; Liu, Guanqiao; Liu, Xiaonan; Zhou, Yangying; Sun, Qi; Zhen, Gehua; Wang, Xiao; Hu, Yihe; Gao, Peisong; Demehri, Shadpour; Cao, Xu; Wan, Mei

doi:10.1172/jci.insight.135446

Cited by 117 publications

(128 citation statements)

References 60 publications

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“…The role of angiogenesis in subchondral bone has been studied recently with genetic mouse models. Su et al ( 2020 ) used transgenic mice to prove that overexpression of platelet-derived growth factor-BB (PDGF-BB) in preosteoclast spontaneously recapitulated the OA-like phenotype in subchondral bone by enhancing both angiogenesis and subchondral bone remodeling; meanwhile, conditional PDGF-BB knockout could effectively prevent surgically-induced OA progression (Su et al, 2020 ). These results suggested that subchondral bone angiogenesis is one of the key processes in subchondral bone remodeling and may be considered as a potential target.…”

Section: Future Therapeutic Targetsmentioning

confidence: 99%

“…Administration of bevacizumab, a neutralizing VEGF antibody, either intra-articularly (1 mL; 25 mg/mL; 3 weeks) or intravenously (5 mg/kg; 2 weeks), has been confirmed to attenuate OA in a rabbit model (Nagai et al, 2014 ). Su et al ( 2020 ) discovered that preosteoclast-derived PDGF-BB enhanced the H type vessel numbers in OA subchondral bone (Kusumbe et al, 2014 ; Su et al, 2020 ). In addition, Hu et al ( 2020 ) reported that H-type vessels and MSCs were coordinated in a positive feedback loop via focal adhesion kinase (FAK) signaling in MSCs, subsequently causing aberrant bone formation in ACLT-induced murine OA subchondral bone (Hu et al, 2020 ); furthermore, the FAK inhibitor defactinib effectively suppressed the positive loop between H type vessels and MSCs, and alleviated OA in mice (Hu et al, 2020 ) ( Table 1 ).…”

Section: Oa Subtypes and Therapeutic Targetsmentioning

confidence: 99%

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Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

Zhu

Chan

Yung

et al. 2021

Front. Cell Dev. Biol.

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There is emerging awareness that subchondral bone remodeling plays an important role in the development of osteoarthritis (OA). This review presents recent investigations on the cellular and molecular mechanism of subchondral bone remodeling, and summarizes the current interventions and potential therapeutic targets related to OA subchondral bone remodeling. The first part of this review covers key cells and molecular mediators involved in subchondral bone remodeling (osteoclasts, osteoblasts, osteocytes, bone extracellular matrix, vascularization, nerve innervation, and related signaling pathways). The second part of this review describes candidate treatments for OA subchondral bone remodeling, including the use of bone-acting reagents and the application of regenerative therapies. Currently available clinical OA therapies and known responses in subchondral bone remodeling are summarized as a basis for the investigation of potential therapeutic mediators.

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Section: Future Therapeutic Targetsmentioning

confidence: 99%

Section: Oa Subtypes and Therapeutic Targetsmentioning

confidence: 99%

Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

Zhu

Chan

Yung

et al. 2021

Front. Cell Dev. Biol.

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“…They produce a very high amount of PDGF-BB, which activates PDGFR-β signaling in a paracrine manner to stimulate subchondral bone angiogenesis along with the osteogenesis coupling process. 143 In addition, treatment with exogenous PDGF-BB or inhibition of cathepsin K (CTSK, a cysteine proteinase highly expressed in osteoclasts) to increase the number of preosteoclasts helps increase type H capillary abundance and attenuate bone loss under osteoporotic conditions. 141 , 144 During the process of angiogenesis, PDGF-BB could directly induce endothelial progenitor cell (EPC) activity.…”

Section: Coupling Of Osteogenesis and Angiogenesismentioning

confidence: 99%

Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis

Chen

Huang

et al. 2021

Bone Res

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Angiogenesis and osteogenesis are coupled. However, the cellular and molecular regulation of these processes remains to be further investigated. Both tissues have recently been recognized as endocrine organs, which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues. This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature. In addition, research progress related to the bone vasculature, vessel-related skeletal diseases, pathological conditions, and angiogenesis-targeted therapeutic strategies are also summarized. With respect to future perspectives, new techniques such as single-cell sequencing, which can be used to show the cellular diversity and plasticity of both tissues, are facilitating progress in this field. Moreover, extracellular vesicle-mediated nuclear acid communication deserves further investigation. In conclusion, a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.

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“…( 135 ) Moreover, abnormally increased PDGF‐BB secretion by preosteoclasts increases type H vessel formation and induces pathological subchondral bone angiogenesis, contributing to OA development. ( 136 ) Likewise, TGFβ mediates signaling cascade to promote recruitment of mesenchymal stem cells and type H vessel formation. ( 137 ) At the same time, Halofuginone attenuates OA by inhibition of TGFβ activity and type H vessel formation in the subchondral bone.…”

Section: Osteoarthritismentioning

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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Angiogenesis stimulated by elevated PDGF-BB in subchondral bone contributes to osteoarthritis development

Cited by 117 publications

References 60 publications

Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

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