BMP 5 Human
Description
Introduction to BMP-5 Human
Bone Morphogenetic Protein-5 (BMP-5) is a member of the transforming growth factor-beta (TGF-β) superfamily, primarily recognized for its role in bone and cartilage formation. In humans, it is encoded by the BMP5 gene on chromosome 6 . BMP-5 belongs to the 60A subgroup of BMPs, which includes BMP-6, BMP-7, and BMP-8, sharing structural and functional similarities . This protein is synthesized as a 454-amino acid precursor, cleaved to form a 20 kDa mature homodimer linked by disulfide bonds .
Molecular Structure
BMP-5 contains seven conserved cysteine residues that form a cysteine-knot domain critical for receptor binding and signaling . Its mature form shares 96% sequence identity with mouse and rat BMP-5, highlighting evolutionary conservation .
| Feature | BMP-5 Human | Other BMPs (e.g., BMP-2, BMP-7) |
|---|---|---|
| Subgroup | 60A | DPP (e.g., BMP-2, BMP-4) or others |
| Primary Role | Dendritic growth, skeletal development | Bone induction, mesoderm patterning |
| Key Receptors | BMPR-IA, BMPR-II | BMPR-IA, BMPR-IB, BMPR-II |
Table 1: Comparative characteristics of BMP-5 and other BMPs .
Signaling Pathways
BMP-5 binds to type I (BMPR-IA) and type II (BMPR-II) receptors, forming hetero-oligomeric complexes. This activates Smad-dependent (e.g., Smad1/5/8) and Smad-independent pathways (e.g., MAPK, PI3K) . These pathways regulate cell proliferation, differentiation, and apoptosis in various tissues.
Developmental and Physiological Functions
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Skeletal Development:
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Neural Development:
Disease-Associated Roles
Table 2: BMP-5’s role in diseases .
3.2.1 Prostate Cancer and Stem Cell Regulation
BMP-5 is critical for maintaining basal stem/progenitor cells in the prostate. Gata3 deficiency increases BMP-5 expression, promoting self-renewal and tumor progression in Pten-deficient models. Inhibiting BMP signaling (e.g., via K02288) delays cancer onset .
3.2.2 Neural Plasticity
BMP-5 induces dendrite formation in sympathetic neurons, with effects blocked by noggin or follistatin . Its expression in the superior cervical ganglia correlates with dendritic expansion during development .
Tissue-Specific Expression
BMP-5 is expressed in:
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Nervous System: Superior cervical ganglia, striatum, and cerebellum .
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Reproductive Organs: Ovarian granulosa cells, regulating progesterone production .
Brain Expression Data
| Brain Region | Expression Level (nTPM) | Species |
|---|---|---|
| Cerebellum | 1.2–3.5 | Human |
| Hippocampus | 0.8–2.1 | Human |
| Brainstem | 0.5–1.8 | Human |
Table 3: BMP-5 expression in human brain regions .
Recombinant Protein Production
BMP-5 is produced via mammalian (e.g., CHO cells) or insect cell systems. Optimization strategies include codon engineering and signal peptide modification to enhance yield and bioactivity .
Clinical Implications
Product Specs
Q&A
What is BMP-5 and what is its basic structure?
BMP-5, or Bone Morphogenetic Protein 5, is a member of the TGF-β superfamily of proteins. The mature protein is formed when the 454 amino acid precursor protein is cleaved at the dibasic cleavage site (RxxR) to release the 20 kDa C-terminal mature protein. Like other BMPs, it contains seven conserved cysteine residues involved in the formation of the cysteine knot and a single interchain disulfide bond. The biologically active form is a disulfide-linked homodimer of the C-terminal mature protein, which is highly conserved across animal species.
How does BMP-5 relate to other BMP family members?
BMP-5 belongs to the 60A subgroup of BMPs, which also includes BMP-6/Vgr-1, BMP-7/OP-1, BMP-8a/OP-2, BMP-8b, and Drosophila 60A. Within this family, BMP-5 shares high sequence homology with BMP-2, BMP-6, and BMP-7. While members of the same subgroup often display conservation of structure and function, they can sometimes elicit distinct cellular responses. For instance, like other members of its subgroup, BMP-5 stimulates dendritic growth in neurons, suggesting functional conservation within the 60A subgroup.
What are the primary tissues where BMP-5 is expressed?
BMP-5 is expressed in multiple tissues throughout development and into adulthood. It is prominently found in chondrocytes within proliferating bone growth plates where it contributes to limb development. Beyond skeletal tissues, BMP-5 is expressed in the lung, liver, trabecular meshwork, and optic nerve head. In the nervous system, BMP-5 is expressed during development and persists into adulthood, with peak expression levels varying by brain region. For example, it shows maximal expression in the hippocampus and cerebellum at E18 through PN1 and again in maturity, while exhibiting peak expression in the adult striatum and brainstem.
How can BMP-5 activity be measured in laboratory settings?
BMP-5 activity can be quantified through its ability to induce alkaline phosphatase production in specific cell lines. For example, researchers commonly measure BMP-5 activity using the ATDC5 mouse chondrogenic cell line, where BMP-5 induces alkaline phosphatase production in a dose-dependent manner. The ED50 (effective dose for 50% maximal response) for this effect is typically less than 0.17 μg/mL. Additionally, neutralization assays using anti-BMP-5 antibodies can confirm the specificity of these effects, with the ND50 (neutralization dose for 50% inhibition) typically between 2-10 μg/mL.
What are the recommended protocols for reconstitution and storage of recombinant BMP-5?
Lyophilized BMP-5 protein should be stored at -20°C. For reconstitution, it is recommended to dissolve the lyophilized protein in sterile H2O to a concentration not less than 100 μg/mL and incubate the stock solution for at least 20 minutes to ensure complete dissolution. After reconstitution, protein aliquots should be stored at -20°C or -80°C to maintain stability. It is advisable to use reconstituted protein within one month. For longer-term storage of the original product, a manual defrost freezer is recommended, and repeated freeze-thaw cycles should be avoided.
What methods are available to study BMP-5 signaling pathways?
BMP-5 signaling can be studied using several approaches. Phosphorylation analysis of Smad-1 transcription factor provides a direct measure of BMP-5 pathway activation, as BMP-5 treatment leads to increased Smad-1 phosphorylation before initiating dendritic growth. Inhibition studies using BMP antagonists like noggin and follistatin or BMPR-IA-Fc chimeric proteins can help delineate receptor specificity and signaling dependencies. RT-PCR and immunocytochemical analyses can be employed to detect BMP-5 mRNA and protein expression in tissues of interest, such as the superior cervical ganglia during dendritic development. For functional studies, in vitro neuron cultures (particularly sympathetic neurons) grown without serum or glial cells provide a clean system to specifically assess BMP-5's dendrite-promoting activity.
How does compound heterozygosity for BMP5 variants affect human development?
Recent research has identified a patient with biallelic loss-of-function variants in BMP5 presenting with a syndromic phenotype including skeletal dysostosis, dysmorphic features, hypermobility, laryngo-tracheo-bronchomalacia, and atrioventricular septal defect. This represents the first human skeletal malformations associated with variants in BMP5. The phenotype correlates with the known tissue-specific expression of BMP5 and resembles morphological abnormalities previously observed in experimental animal models. These findings suggest that BMP5 variants can lead to a range of developmental anomalies involving ears, heart, and skeleton, providing new insights into BMP5's role in human development. This research direction is particularly important as most BMP-related genetic skeletal disorders have been limited to BMP1, BMP2, BMPR1B, and BMPER.
How does BMP-5 signaling interact with other developmental pathways?
BMP-5 interacts with multiple signaling pathways during development. Like other BMPs, BMP-5 is inhibited by chordin and noggin, which are critical for establishing morphogen gradients during embryonic development. BMP-5 has been implicated in dorsal forebrain patterning, as evidenced by its expression in the dorsal midline of the developing forebrain and observations that ectopic expression of BMP-5 in the developing neural tube downregulates ventral markers while maintaining dorsal markers. Studies of Bmp5/Bmp7 double mutants further support BMP-5's role in early forebrain development. Additionally, BMP-5's effects on bone and cartilage development involve complex interactions with other developmental signals, including those in the TGF-β superfamily. Understanding these pathway interactions is crucial for unraveling the multifaceted roles of BMP-5 in tissue development and homeostasis.
What are the potential roles of BMP-5 in glaucoma pathogenesis?
BMP-5 is expressed in the trabecular meshwork and optic nerve head, suggesting potential roles in the development and normal function of these ocular structures. Research indicates that BMP-5 may act as an important signaling molecule within these tissues, potentially contributing to glaucoma pathogenesis. The trabecular meshwork is critical for regulating intraocular pressure, dysfunction of which is a primary risk factor for glaucoma development. Understanding how BMP-5 signaling influences trabecular meshwork function and optic nerve head biology could provide insights into glaucoma mechanisms and potential therapeutic approaches. Research in this area may include examining BMP-5 expression in normal versus glaucomatous eyes, the effects of modulating BMP-5 signaling on intraocular pressure, and genetic association studies of BMP5 variants with glaucoma risk.
How might BMP-5 contribute to certain cancers?
BMP-5 may play roles in certain cancers, although the specific mechanisms and cancer types require further investigation. As a member of the TGF-β superfamily, BMP-5 has the potential to influence cell proliferation, differentiation, migration, and apoptosis—processes that are frequently dysregulated in cancer. Research questions in this area may explore BMP-5 expression patterns in different cancer types, the impact of BMP-5 signaling on cancer cell behavior, potential correlations between BMP5 genetic variants and cancer susceptibility, and the therapeutic potential of targeting BMP-5 pathways in cancer treatment. Additionally, given BMP-5's role in bone development, its involvement in bone metastases of various cancers represents another important avenue for investigation.
What are the therapeutic applications of PODS® Human BMP-5 technology?
PODS® (Polyhedrin Delivery System) Human BMP-5 represents an advanced delivery technology for this growth factor. PODS® proteins are produced using an insect cell expression system where the active protein is co-expressed with polyhedrin carrier protein, forming microcrystals that capture the active protein in its natively folded form. This technology offers several therapeutic advantages: it limits proteolytic degradation, preserves bioactivity, provides sustained release of the protein, and enables functionalization of surfaces. Potential therapeutic applications include bone and cartilage regeneration, neural tissue engineering, and targeted delivery of BMP-5 to specific tissues. Research questions may address optimization of release kinetics for different applications, comparison with conventional delivery methods, tissue-specific targeting strategies, and clinical outcomes in various regenerative medicine contexts.
Product Science Overview
Bone Morphogenetic Protein-5 (BMP-5) is a member of the bone morphogenetic protein family, which is part of the transforming growth factor-beta (TGF-β) superfamily. BMPs are known for their ability to induce bone and cartilage development. BMP-5, in particular, plays a crucial role in tissue development, repair, and regeneration .
BMPs were initially identified by their ability to induce endochondral osteogenesis in vivo in an extraskeletal site. This discovery was made by Professor Marshall Urist and Professor Hari Reddi . BMP-5 is an essential signaling molecule within the trabecular meshwork and optic nerve head, and it may play a potential role in glaucoma pathogenesis .
BMP-5 is a protein encoded by the BMP5 gene in humans. The human recombinant form of BMP-5 is produced in Escherichia coli (E. coli) and is a single, non-glycosylated polypeptide chain containing 139 amino acids, with a total molecular mass of 15.7 kDa . The protein is purified using proprietary chromatographic techniques to ensure high purity and stability .
Recombinant human BMPs (rhBMPs) are used in various orthopedic applications, such as spinal fusions, nonunions, and oral surgery. BMP-5 has been shown to increase the levels of osteopontin, BMP-2, alkaline phosphatase, and core binding factor alpha 1 mRNAs in human periodontal ligament cells . This makes it a promising candidate for tissue engineering and regenerative medicine.
The BMP-5 human recombinant protein is formulated in a sterile, filtered colorless solution containing 10mM Sodium Citrate buffer (pH 3.5) and 10% Glycerol. It is recommended to store the protein at 4°C if it will be used within 2-4 weeks, or frozen at -20°C for longer periods. For long-term storage, adding a carrier protein (0.1% HSA or BSA) is advised to avoid multiple freeze-thaw cycles .
