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Theranostics 2020; 10(1):426-436. doi:10.7150/thno.34126 This issue Cite

Review

Type H blood vessels in bone modeling and remodeling

Yi Peng¹, Song Wu¹, Yusheng Li^2✉, Janet L. Crane^3✉

1. Department of Orthopedic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.
2. Department of Orthopedic Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 41000, China.
3. Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

✉ Corresponding author: Yusheng Li, E-mail: liyushengedu.cn Janet L. Crane, E-mail: jcrane2edu

Abstract

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.

Keywords: Type H vessels, H-type vessels, CD31^hiEmcn^hi endothelial cells, Angiogenesis, Osteogenesis, Bone formation

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