Bone Morphogenetic Proteins: A critical review

The role of bone morphogenetic proteins in myeloma cell survival

“…[1][2][3] Also in multiple myeloma, BMP signaling has been proposed to influence important processes such as growth control, bone homeostasis, iron metabolism and angiogenesis. However, BMP signaling is highly dependent on cell type and context.…”

“…The bone inducing activity of BMP was discovered in the 1960s and the first proteins of the family were characterized in the late 1980s. [5,6] Further studies have revealed multiple functions for BMPs, such as involvement in embryogenesis, hematopoiesis and neurogenesis (reviewed by Bragdon et al), [2] as well as both tumor promoting and growth inhibiting effects in various cancers. [3] The signal is usually transduced through the (small) mothers against dpp (decapentaplegic) homolog (SMAD) pathway that is unique for the TGF-β family.…”

“…This is achieved by multiple regulatory mechanisms, including regulation of ligand activity, availability of ligand, particularly regulated by highly specific antagonists, expression of receptors, decoy receptors, co-receptors and the inhibitory (I)-SMADs, SMAD6 and SMAD7. [2] …”

Osteoinductive signals and heterotopic ossification

“…(5) BMPs are members of the transforming growth factor b (TGF-b) family of signaling proteins that regulates a wide range of cellular activity, including differentiation, proliferation, apoptosis, migration, positional information, and stem cell renewal, in addition to key functions in embryonic development and skeletal formation. (6) It is generally accepted that changes in the tissue microenvironment that are conducive to support the induction and progression of bone formation are required; for example, inflammation, angiogenesis, hypoxia, extracellular matrix, and mechanical forces all have been implicated in directing osteogenesis. (3,(6)(7)(8) However, the cellular and molecular mechanisms that are activated through these tissue changes remain largely undetermined.…”

“…(6) It is generally accepted that changes in the tissue microenvironment that are conducive to support the induction and progression of bone formation are required; for example, inflammation, angiogenesis, hypoxia, extracellular matrix, and mechanical forces all have been implicated in directing osteogenesis. (3,(6)(7)(8) However, the cellular and molecular mechanisms that are activated through these tissue changes remain largely undetermined. In this issue of the Journal of Bone and Mineral Research, Leblanc and colleagues (9) move us a step closer to being able to elucidate factors within the cellular environment that regulate cell differentiation to form bone tissue through their study investigating potential osteoprogenitor cells and requirements for specific tissue microenvironments that contribute to the pathophysiology of BMP-induced heterotopic ossification.…”