BMP13 is a homodimeric protein synthesized as a preproprotein containing a pro-domain and an active C-terminal domain . Key structural features include:
The mature protein adopts a cysteine knot tertiary structure, typical of TGF-β family members, enabling receptor binding and signal transduction . Recombinant BMP13 is produced in Escherichia coli or mammalian systems, with >95% purity confirmed via SDS-PAGE and HPLC .
Inhibition of Osteogenic Differentiation: BMP13 suppresses alkaline phosphatase (ALP) activity and matrix mineralization in human bone marrow mesenchymal stromal cells (BM MSCs), contrasting with pro-osteogenic BMP2/7 .
Promotion of Chondrogenesis: Increases proteoglycan synthesis and collagen II expression in tendon fibroblasts and chondrocytes .
Tendon/Ligament Healing: Accelerates collagen fiber organization and mechanical strength in damaged tendons .
Hepatic Fibrosis: Activates hepatic stellate cells (HSCs) via Smad1/5/9 and ERK pathways, upregulating profibrotic markers (e.g., COL1A1, α-SMA) .
Essential for embryonic skeletal patterning, joint formation, and neural plate development .
Mutations linked to Klippel-Feil Syndrome (spinal fusion) and ocular colobomata .
BMP13 signals through BMPRIA/IB and BMPRII receptors, activating Smad1/5/8 and non-canonical pathways (e.g., ERK) :
Tissue Engineering: Enhances cartilage repair and tendon regeneration in preclinical models .
Antifibrotic Target: Inhibition reduces COL1A1 and α-SMA in HSCs, suggesting potential in treating liver fibrosis .
Recombinant BMP13 is optimized for research use:
Bone Morphogenetic Protein-13 (BMP-13), also known as Growth Differentiation Factor 6 (GDF6), is a member of the bone morphogenetic protein family, which is part of the larger transforming growth factor-beta (TGF-β) superfamily . BMP-13 plays a crucial role in tissue development, regeneration, and repair, particularly in the skeletal, nervous, and muscular systems .
BMPs were initially identified as proteins capable of inducing ectopic bone formation when implanted into the muscle of adult rats . BMP-13, specifically, has been studied for its role in cartilage and bone repair . It is involved in regulating apoptosis during retinal development and controls proliferation and cellular differentiation in the retina and bone formation .
BMP-13 exerts its biological activity through combinations of type I and type II serine/threonine kinase receptors . The precursor proteins are synthesized and then proteolytically cleaved within the cell to yield the active, carboxy-terminal mature protein dimer . These dimers bind to receptors on the surface of mesenchymal stem cells, initiating a cascade of events that lead to their differentiation into bone- and cartilage-forming cells .
Altered BMP signaling pathways are associated with several human diseases, including arthritis, osteoporosis, kidney diseases, cancer, and pulmonary hypertension . Recombinant BMP-13 has been explored for its potential therapeutic applications in bone and cartilage repair . However, it is also important to note that BMP-13 has been reported to have protumorigenic effects in certain contexts .