Bone Morphogenetic Proteins

Abstract

Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily, acting as potent regulators during embryogenesis and bone and cartilage formation and repair. Cell and molecular biology approaches have unveiled the great complexity of BMP action, later confirmed by transgenic animal studies. Genetic engineering allows for the production of large amounts of BMPs for clinical use, but they have systematically been associated with a delivery system, such as type I collagen and calcium phosphate ceramics, to ensure controlled release and to maximize their biological activity at the surgical site, avoiding systemic diffusion. Clinical orthopedic studies have shown the benefits of FDA-approved recombinant human BMPs (rhBMPs) 2 and 7, but side effects, such as swelling, seroma, and increased cancer risk, have been reported, probably due to high BMP dosage. Several studies have supported the use of BMPs in periodontal regeneration, sinus lift bone-grafting, and non-unions in oral surgery. However, the clinical use of BMPs is growing mainly in off-label applications, with robust evidence to ascertain rhBMPs' safety and efficacy through well-designed, randomized, and double-blind clinical trials. Here we review and discuss the critical data on BMP structure, mechanisms of action, and possible clinical applications.

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

“…BMPs have been the subject of other recent and extensive reviews (Chen et al 2012). Genetic manipulation of mice has allowed a wealth of knowledge to be obtained regarding the complexity of BMPs that may have clinical relevance, such as in the treatment and clinical management of bone grafting and non-unions (reviewed in Carreira et al (2014)). Roles of BMPs in adipogenesis and energy metabolism have recently been described, including in adipocyte development, adipose cell fate determination, differentiation of committed preadipocytes and function of mature adipocyte (Tang et al 2004, Taha et al 2006, Huang et al 2009).…”

A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs

“…For example, BMP2/4 can induce adipocytic lineage commitment of MSCs through activation of p38 Smad/MAPK signalling 9, 10, 11. In addition, other side effects, such as increased cancer risk related to higher BMP doses, have also been reported 12. The above studies indicate that enhancing pro‐osteogenic and blocking pro‐adipogenic effects with a lower dose of BMPs may be effective for clinical use of BMPs in bone disorders.…”

The Role of Signaling Pathway on Osteoprogenitor Cell Behavior and Bone Formation

“…TGF-β acts through the heteromeric receptor complex, comprised of type I and type II receptors at the cell surface that transduces intracellular signals by Smad complex or MAPK cascade (12)(13)(14)(15)(16)(17). At least 29 and probably up to 42 TGF-β, five type II receptors and seven type I receptors are encoded by the human genome (18,19). Signals transduced by TGF-β superfamily members control the formation of tissue differentiation, through their effects on cell proliferation, differentiation, and migration (20)(21)(22)(23).…”