title: Bone morphogenetic proteins: facts, challenges, and future perspectives.
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.
authors.affiliation: Biochemistry Department, Chemistry Institute, and Cell and Molecular Therapy Center NUCEL-NETCEM, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Carreira
authors.forename: F H
authors.initials: FH
authors.lastname: Lojudice
authors.forename: E
authors.initials: E
authors.lastname: Halcsik
authors.forename: R D
authors.initials: RD
authors.lastname: Navarro
authors.forename: M C
authors.initials: MC
authors.lastname: Sogayar
authors.forename: J M
authors.initials: JM
authors.lastname: Granjeiro
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use; D055419:Bone Morphogenetic Protein 7 / Q000627:therapeutic use; D019485:Bone Morphogenetic Proteins / Q000502:physiology* / Q000627:therapeutic use; D001861:Bone Regeneration / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D016212:Transforming Growth Factor beta / Q000627:therapeutic use
chemical_list: C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2
keywords: bioengineering; biomaterial(s); bone remodeling/regeneration; growth factor(s); regenerative medicine; systematic reviews and evidence-based medicine