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.
Highlights
Osteoporosis is a common systemic bone metabolism disorder characterized by decreased bone mass and disruption of the fine structure of bone tissue, which further results in increased bone fragility and occurrence of fracture (McGowan, 1993)
It has been shown that Smad protein is the key intermediates of canonical transforming growth factor-beta (TGF-β) signaling pathway and bone morphogenetic protein (BMP) pathway, which are important pathways that regulate bone homeostasis (SánchezDuffhues et al, 2015)
Through genetic screening of drosophila, it was discovered that the mothers against decapentaplegic’ (Mad) polypeptide, which is downstream of the transforming growth factor-β (TGF-β) family signaling pathway, has a highly conserved and unknown domain that was demonstrated to have high similarity with 3 types of peptides isolated from nematodes, cem-1, cem-2 and cem-3 (Sekelsky et al, 1995; Raftery and Sutherland, 1999)
Summary
Osteoporosis is a common systemic bone metabolism disorder characterized by decreased bone mass and disruption of the fine structure of bone tissue, which further results in increased bone fragility and occurrence of fracture (McGowan, 1993). Bone is a dynamic active tissue that needs to maintain the balance of bone mineralization and the integrity of bone structure through continuous remodeling (Lemaire et al, 2004). Bone formation and bone resorption maintain a dynamic balance, which is called bone homeostasis. It was previously shown that dysregulated Smad signaling pathway resulted in a number of bone disorders in humans (Liu et al, 2013). It has been shown that Smad protein is the key intermediates of canonical transforming growth factor-beta (TGF-β) signaling pathway and bone morphogenetic protein (BMP) pathway, which are important pathways that regulate bone homeostasis (SánchezDuffhues et al, 2015). We attempted to shed light on recent studies of the effect of Smad signaling pathway in bone remodeling. Afterward we discuss the potential use of Smad for the treatment of osteoporosis
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