TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation.

Bone Res

Tissue Banking and Biomaterial Research Unit, Atomic Energy Research Establishment , Dhaka 1349, Bangladesh.

Published: August 2015

AI Article Synopsis

  • TGF-β/BMP is crucial for bone formation, with its activity affecting a range of health issues such as skeletal abnormalities and cancer.
  • Alterations in this signaling pathway involve the phosphorylation of receptors that activate Smads, which transmit TGF-β/BMP signals, and are influenced by factors like the transcription factor Runx2.
  • The interaction of TGF-β/BMP with other pathways (e.g., MAPK, Wnt) creates a complex regulatory network in bone dynamics, positioning Runx2 as a key integrator of these signals.

Article Abstract

Transforming growth factor-beta (TGF-β)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and β-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472151PMC
http://dx.doi.org/10.1038/boneres.2015.5DOI Listing

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