BMP13 Human

Bone Morphogenetic protein-13 Human Recombinant
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Description

Molecular Structure and Characteristics

BMP13 is a homodimeric protein synthesized as a preproprotein containing a pro-domain and an active C-terminal domain . Key structural features include:

PropertyDetails
Molecular Weight~27 kDa (homodimer of two 120–121 amino acid chains)
Disulfide Bonds7 conserved cysteine residues forming intra-/inter-chain bonds
Active Domain Conservation>95% sequence homology across vertebrates (e.g., zebrafish to humans)
Proteolytic Cleavage SitesRXXR consensus site for serine proteases (e.g., furin)

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 .

Chondrogenesis and Osteogenesis Regulation

  • 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 .

Tissue Repair and Fibrosis

  • 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) .

Developmental Roles

  • Essential for embryonic skeletal patterning, joint formation, and neural plate development .

  • Mutations linked to Klippel-Feil Syndrome (spinal fusion) and ocular colobomata .

Signaling Mechanisms

BMP13 signals through BMPRIA/IB and BMPRII receptors, activating Smad1/5/8 and non-canonical pathways (e.g., ERK) :

  1. Receptor Binding: Preferential affinity for BMPRIB (ALK6) over BMPRIA .

  2. Downstream Effects:

    • Phosphorylated Smads translocate to the nucleus, inducing target genes (e.g., ID1) .

    • Synergistic modulation of other BMPs (e.g., upregulates BMP4, suppresses BMP6) .

Disease Associations

ConditionMechanismReference
Klippel-Feil SyndromeMutations in BMP13 pro-domain disrupt skeletal segmentation
Liver CirrhosisBMP13 overexpression in activated HSCs drives fibrosis
Hepatocellular CarcinomaStroma-derived BMP13 promotes tumor progression

Therapeutic Applications

  • 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 .

Production and Activity Assays

Recombinant BMP13 is optimized for research use:

ParameterSpecification
Expression SystemE. coli or mammalian cells
Activity (ED50)63–240 ng/mL (alkaline phosphatase induction in ATDC5 cells)
StorageLyophilized at -20°C; reconstituted in sterile H2O (≥100 μg/mL)

Research Gaps and Future Directions

  • Structural Studies: Full 3D structure of BMP13 remains unresolved .

  • Dose-Dependent Effects: Dual roles in tumor promotion vs. tissue repair require further exploration .

  • Clinical Trials: No human trials to date; safety and efficacy in regenerative therapies unverified .

Product Specs

Introduction
Growth/differentiation factors (GDF1-GDF15), part of the transforming growth factor beta (TGF-β) superfamily, play crucial roles in embryonic development and tissue homeostasis. Among them, BMP13, also known as Growth Differentiation Factor 6 (GDF6), is particularly important for skeletal development and joint formation. BMP13 regulates chondrocyte proliferation and differentiation, influencing bone and cartilage formation. Mutations in the BMP13 gene have been associated with skeletal disorders, highlighting its significance in skeletal health.
Description
Recombinant human BMP13, expressed in E. coli, is a non-glycosylated homodimeric protein linked by disulfide bonds. Each subunit comprises 120 amino acids, contributing to a total molecular weight of 27.1 kDa. The protein undergoes purification using proprietary chromatographic techniques to ensure high purity.
Physical Appearance
Sterile Filtered White lyophilized (freeze-dried) powder.
Formulation
The BMP-13 protein was subjected to lyophilization from a 0.2µm filtered solution concentrated in 30% Acetonitrile and 0.1% TFA.
Solubility
For reconstitution, it is recommended to dissolve the lyophilized BMP13 in sterile 18M-cm H2O at a minimum concentration of 100µg/ml. This solution can be further diluted in other aqueous solutions as required.
Stability
While lyophilized BMP13 remains stable at room temperature for up to 3 weeks, it is recommended to store it desiccated below -18°C. Once reconstituted, the BMP-13 solution should be stored at 4°C for 2-7 days. For long-term storage, freezing below -18°C is recommended. To enhance stability during long-term storage, consider adding a carrier protein such as 0.1% HSA or BSA. Avoid repeated freeze-thaw cycles to preserve protein integrity.
Purity
The purity of this product exceeds 95.0%, as determined by the following methods: 
(a) High-Performance Liquid Chromatography (HPLC) analysis. 
(b) Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) analysis.
Biological Activity
The biological activity of this product is determined by its ability to induce alkaline phosphatase production in murine ATDC5 cells. The ED50, representing the concentration at which 50% of the maximal response is observed, is less than 2.0µg/ml. This corresponds to a specific activity greater than 500IU/mg.
Synonyms
Growth Differentiation Factor 6, Growth/Differentiation Factor 16, Bone Morphogenetic Protein 13, BMP-13, BMP13, GDF-6, Klippel-Feil Malformation, Segmentation Syndrome 1, Klip-Feil Malformation, Klippel-Feil Syndrome, MCOPCB6, SCDO4, CDMP2, LCA17, MCOP4, GDF16, KFS1, KFSL, SGM1, KFM, KFS, GDF6.
Source
Escherichia Coli.
Amino Acid Sequence
TAFASRHGKR HGKKSRLRCS KKPLHVNFKE LGWDDWIIAP LEYEAYHCEG VCDFPLRSHL EPTNHAIIQT LMNSMDPGST PPSCCVPTKL TPISILYIDA GNNVVYKQYE DMVVESCGCR.

Product Science Overview

Introduction

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 .

Discovery and Function

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 .

Mechanism of Action

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 .

Clinical Implications

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 .

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