BMP signaling represents a fundamental signaling profile in periosteal effects

BMP signaling represents a fundamental signaling profile in periosteal effects. BMP2 signaling is proposed to function downstream of PTH and the canonical Wnt signaling pathway during bone growth and fracture repair. During bone formation and fracture healing, BMP2 signaling specifically acts on PDPCs (blue pathway). After ligand binding, phosphorylated (P) BMPR-II helps to phosphorylate BMPR-I. Activated BMPR-I recruits and phosphorylates pathway-specific receptor activated Smads (Smad1/5/8), which can form trimers with Smad4 and translocate into the nucleus. Inside the nucleus, the Smad trimerization recruits and/or integrates with cell type specific transcription factors and then regulates target gene expression. Thereby, BMP2 signaling increases periosteal osteogenesis and chondrogenesis. When PDCs respond to mechanical stretch, the expressions of BMP2 and BMP4 increase, while BMP6 expression is suppressed. BMP-6, in turn, induces the expressions of IL1β and IL6, which promote osteoclast differentiation through the RANKL-dependent pathway (green pathway). In this way, PDCs sense mechanical stress and promote osteogenesis but decrease osteoclastogenesis. PTH: parathyroid hormone; SOST-ab: sclerostin neutralizing antibody; BMP: bone morphogenetic protein; BMPR-I: type I BMP receptor; BMPR-II: type II BMP receptor; RANKL: receptor activator of nuclear factor κ-B ligand; RANK: receptor activator of nuclear factor κ-B; P: phosphorylation

Publication

Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration (2024) Xinyuan Zhang, et al. Int J Mol Sci. 2024 Feb;25(4). Figure: F1. Homo sapiens

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