title: Angiogenic factors in bone local environment.
abstract: Angiogenesis plays an important role in physiological bone growth and remodeling, as well as in pathological bone disorders such as fracture repair, osteonecrosis, and tumor metastasis to bone. Vascularization is required for bone remodeling along the endosteal surface of trabecular bone or Haversian canals within the cortical bone, as well as the homeostasis of the cartilage-subchondral bone interface. Angiogenic factors, produced by cells from a basic multicellular unit (BMU) within the bone remodeling compartment (BRC) regulate local endothelial cells and pericytes. In this review, we discuss the expression and function of angiogenic factors produced by osteoclasts, osteoblasts and osteocytes in the BMU and in the cartilage-subchondral bone interface. These include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), BMP7, receptor activator of NF-κB ligand (RANKL) and epidermal growth factor (EGF)-like family members. In addition, the expression of EGFL2, EGFL3, EGFL5, EGFL6, EGFL7, EGFL8 and EGFL9 has been recently identified in the bone local environment, giving important clues to their possible roles in angiogenesis. Understanding the role of angiogenic factors in the bone microenvironment may help to develop novel therapeutic targets and diagnostic biomarkers for bone and joint diseases, such as osteoporosis, osteonecrosis, osteoarthritis, and delayed fracture healing.
authors.affiliation: Molecular Lab, School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA 6009, Australia.
authors.forename: Shek Man
authors.initials: SM
authors.lastname: Chim
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tickner
authors.forename: Siu To
authors.initials: ST
authors.lastname: Chow
authors.forename: Vincent
authors.initials: V
authors.lastname: Kuek
authors.forename: Baosheng
authors.initials: B
authors.lastname: Guo
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Vicki
authors.initials: V
authors.lastname: Rosen
authors.forename: Wendy
authors.initials: W
authors.lastname: Erber
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D001846:Bone Development; D055419:Bone Morphogenetic Protein 7 / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic; D053245:RANK Ligand / Q000502:physiology
chemical_list: D043925:Angiogenesis Inducing Agents; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D004815:Epidermal Growth Factor
keywords: Angiogenesis; Bone remodeling; Bone remodeling compartment; EGF-like