A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis. This product encodes human BPM7 and is expressed in CHO.
>99% by SDS-Page and HPLC analysis
<0.001 EU per 1 μg of the peptide by the LAL method
Discovered in the early 1990s, Bone Morphogenetic Protein 7 (BMP7) is a member of the Transforming Growth Factor-Beta (TGF-β) superfamily known for its essential role in embryonic development and tissue homeostasis. Located on the gene locus of 20q13, BMP7, also known as osteogenic protein-1 (OP-1), encodes a protein that was originally discovered for its ability to induce bone and cartilage development.
The protein structure of BMP7 is characterized by a cysteine-knot motif, which forms a strong bond for the formation of a homodimer or a heterodimer. This protein, encoded by the BMP7 gene, is processed to its mature form within the body following cleavage of an initial signal sequence.
In terms of function, BMP7 is recognized for its crucial role in body development and maintenance. It plays a significant role in the development of kidney, eye, teeth, and bone. It also induces cartilage and bone formation, enhances calcium deposition in bones and assists in the process of neural induction. In the mature organism, BMP7 helps in maintaining the physiological balance of different organs including the kidney, where it prevents the development of renal fibrosis, and in the bone, where it helps in maintaining bone mass.
BMP7 – related Signaling Pathways
BMP7 engages with two types of serine/threonine kinase receptors, Type I and Type II, leading to the activation of several signaling pathways. The most significant pathway activated by BMP7 is the Smad pathway. In this pathway, BMP7 binds to its receptors leading to the recruitment and phosphorylation of Smad proteins - Smad1, Smad5, and Smad8. Furthermore, BMP7 is also involved in non-Smad pathways such as MAPK, PI3K/Akt, and JNK pathways.
In the Smad pathway, after the Smad proteins are phosphorylated by the BMP7 receptor complex, they combine with Smad4 and move into the nucleus where they regulate gene transcription. This process impacts cellular functions like differentiation, proliferation, and apoptosis.
The MAPK pathway, activated by BMP7, is involved in cellular responses to a diverse array of stimuli such as mitogens, osmotic stress, heat shock, and proinflammatory cytokines. PI3K/Akt pathway, on the other hand, regulates key cellular functions such as transcription, translation, growth, and survival.
BMP7 related Diseases and its Role
Given its significant functions, an aberration in BMP7 expression leads to various developmental disorders and diseases. Reduced BMP7 expression is associated with diseases like chronic kidney disease, osteoarthritis, and cancer. It has been observed that BMP7 levels are decreased in patients with retinal degenerative disorders. Importantly, BMP7 also carries therapeutic potentials for disorders like renal fibrosis, osteoporosis, and other skeletal defects.
Application of BMP7 in Medicine
In the field of medicine, the therapeutic potential of BMP7 is increasingly acknowledged. BMP7, by promoting bone regeneration, has been used in treating bone defects and fractures. It has also shown potential in treating diabetic nephropathy and renal fibrosis by inhibiting the TGF-β1-dependent epithelial-mesenchymal transition. Additionally, recombinant human BMP7, also known as rhBMP7 or OP-1, has been utilized in surgical applications for bone repair and restoration.
Drug Candidates related to BMP7
At present, there are various drug candidates involving BMP7 under investigation. These include LY2109761 and LDN193189. LY2109761 is a novel TGFβ receptor type I and type II dual inhibitor, which can counteract the inhibition of BMP signaling. Meanwhile, LDN193189 a small molecule that selectively inhibits BMP type I receptors, effectively restricting BMP signaling.
The increasing understanding of BMP7, its signaling pathways, and its role in disease occurrence have opened up promising avenues for therapeutic uses. With ongoing research, the full medical potential of BMP7 is yet to be completely unraveled.
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