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Review
. 2021 May 5:8:593310.
doi: 10.3389/fmolb.2021.593310. eCollection 2021.

The Smad Dependent TGF-β and BMP Signaling Pathway in Bone Remodeling and Therapies

Ming-Li Zou  1   2 , Zhong-Hua Chen  3 , Ying-Ying Teng  2 , Si-Yu Liu  1   2 , Yuan Jia  1   2 , Kai-Wen Zhang  1   2 , Zi-Li Sun  1   2 , Jun-Jie Wu  2 , Zheng-Dong Yuan  2 , Yi Feng  2 , Xia Li  2 , Rui-Sheng Xu  2 , Feng-Lai Yuan  2
Affiliations
Review

The Smad Dependent TGF-β and BMP Signaling Pathway in Bone Remodeling and Therapies

Ming-Li Zou et al. Front Mol Biosci. .

Abstract

Bone remodeling is a continuous process that maintains the homeostasis of the skeletal system, and it depends on the homeostasis between bone-forming osteoblasts and bone-absorbing osteoclasts. A large number of studies have confirmed that the Smad signaling pathway is essential for the regulation of osteoblastic and osteoclastic differentiation during skeletal development, bone formation and bone homeostasis, suggesting a close relationship between Smad signaling and bone remodeling. It is known that Smads proteins are pivotal intracellular effectors for the members of the transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMP), acting as transcription factors. Smad mediates the signal transduction in TGF-β and BMP signaling pathway that affects both osteoblast and osteoclast functions, and therefore plays a critical role in the regulation of bone remodeling. Increasing studies have demonstrated that a number of Smad signaling regulators have potential functions in bone remodeling. Therefore, targeting Smad dependent TGF-β and BMP signaling pathway might be a novel and promising therapeutic strategy against osteoporosis. This article aims to review recent advances in this field, summarizing the influence of Smad on osteoblast and osteoclast function, together with Smad signaling regulators in bone remodeling. This will facilitate the understanding of Smad signaling pathway in bone biology and shed new light on the modulation and potential treatment for osteoporosis.

Keywords: Smad signaling pathway; bone morphogenetic proteins; bone remodeling; osteoporosis; transforming growth factor-β.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Activation of TGF-β/Smad and BMP/Smad pathways leading to Smad -mediated gene expression.
FIGURE 2
FIGURE 2
TGF-β/Smad signaling during osteoclast differentiation. The activation of Smad 2/3 by TGF-β, and Smad 2/3 binds directly to TRAF6-TAB1-TAK1 to form a complex that can promote RANKL-induced osteoclast differentiation.
See this image and copyright information in PMC

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