TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation

Abstract

Transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-β/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-β/BMPs is specifically through both canonical Smad-dependent pathways (TGF-β/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-β/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-β/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-β/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-β/BMP signaling. This review also highlights the different modes of cross-talk between TGF-β/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation.

Coleusin Factor, a Novel Anticancer Diterpenoid, Inhibits Osteosarcoma Growth by Inducing Bone Morphogenetic Protein-2–Dependent Differentiation

“…4). BMPs play important roles in regulating osteogenic maturation and bone formation (14). Among the BMPs tested in our experiments, only BMP-2 expression was significantly increased after Coleusin factor treatment.…”

“…Activation of BMP receptors triggers phosphorylation of Smad1 and Smad5, which subsequently combine with Smad4. The Smad complexes translocate into nucleus and interact with RUNX2 to induce osteoblast-specific gene expression (14,43). RUNX2 is a critical transcription factor in osteogenesis.…”

“…BMPs play important roles in bone tissue formation and remodeling (12)(13)(14). Compared with the other BMP members, BMP-2 is a dominant factor in postnatal skeletal homeostasis (15).…”

The roles of immune cells in bone healing; what we know, do not know and future perspectives

“…Several growth factors are needed to support bone healing particularly during the repair phase including platelet-derived growth factor (PDGF), TGF-b, Insulin-like growth Factor (IGF), fibroblast growth factor-1 (FGF-1) and BMPs that promote the proliferation and the chondrogenic differentiation of MSCs as well as deposition of collagen [49,89,90]. Overall, the conversion of soft callus into hard callus is highly controlled by macrophages, T-and B-lymphocytes and various cytokines and growth factors demonstrating the continuation of immune-bone interactions even after the end of the inflammation phase.…”

The role of p38 signaling and poly(ADP-ribosyl)ation-induced metabolic collapse in the osteogenic differentiation-coupled cell death pathway

“…In turn, mineralization (deposition of calcium, magnesium, and phosphate containing hydroxyapatite) completes the process resulting in a bone tissue that is hard and strong enough to fulfill skeletal function [2]. This complex series of events is regulated by a diverse set of transcription factors such as osterix, Runx2, Groucho/TLE, or Twist and soluble morphogenic factors such as BMPs, TGFβ, and Wnt [3][4][5][6].…”