BMP5

Fig1. Representative members of the BMP signaling pathway that have been demonstrated to cause or be associated with human diseases. (Richard N Wang, 2014)

What is BMP5 protein?

BMP5 (bone morphogenetic protein 5) gene is a protein coding gene which situated on the short arm of chromosome 6 at locus 6p12. This gene encodes a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. The superfamily includes large families of growth and differentiation factors. Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. These proteins are synthesized as prepropeptides, cleaved, and then processed into dimeric proteins. This protein may act as an important signaling molecule within the trabecular meshwork and optic nerve head, and may play a potential role in glaucoma pathogenesis. The BMP5 protein is consisted of 454 amino acids and its molecular mass is approximately 51.7 kDa.

What is the function of BMP5 protein?

BMP5 is a growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cartilage and bone formation or neurogenesis. It initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. BMP5 can also signal through non-canonical pathway such as MAPK p38 signaling cascade to promote chondrogenic differentiation. It can also promote the expression of HAMP which is repressed by its interaction with ERFE.

BMP5 Related Signaling Pathway

BMP5 can activate the PI3K/Akt signaling pathway by activating BMP receptors. BMP5 can activate the JNK (c-Jun N-terminal kinase) signaling pathway by activating both SMAD-dependent and non-dependent signaling pathways. Or form complexes with activated Smad proteins that bind to Smad4 into the nucleus and regulate the transcription of target genes. At the same time, there is cross-regulation between BMP5 and Wnt signaling pathways.

BMP5 Related Diseases

Mutations or abnormalities in the function of BMP5 can lead to developmental defects in the heart, such as ventricular septal defects and patent ductus arteriosus. Defects in BMP5 may lead to abnormal bone development, such as impaired fracture healing and decreased bone density. The abnormal expression of BMP5 may be related to the occurrence and development of cataract.

Bioapplications of BMP5

By combining BMP5 with scaffolds, tissue engineered bone with good biocompatibility and osteogenic activity can be prepared for repairing bone defects. In addition, BMP5 can also be used in cartilage tissue engineering, periodontal tissue regeneration and other aspects. BMP5 gene therapy is a new therapeutic method, by introducing BMP5 gene into target cells, it makes them express BMP5 protein in vivo, so as to play a therapeutic role.

Case study 1: Lijun Zhang, 2015

Fibroblast activation and proliferation are important for fibroblast-myofibroblast transdifferentiation, a crucial process in the pathological changes that define renal interstitial fibrosis. The left-right determination factor (Lefty) is an important cytokine of the transforming growth factor (TGF)-β family, with two variants, Lefty-1 and Lefty-2, in mice which can inhibite the TGF-β1 signaling. However, whether Lefty-1 influences fibroblast activation and proliferation, and consequently prevents fibroblast-myofibroblast transdifferentiation, remains unclear.

This study aimed to investigate whether Lefty-1 can attenuate TGF-β1-induced fibroblast-myofibroblast transdifferentiation in normal rat kidney interstitial fibroblast cells (NRK-49F), as well as the mechanisms underlying any effects. The results show lefty-1 induced remarkable reductions in TGF-β1-induced Smad3 and mitogen-activated protein kinase-10/c-Jun N-terminal kinase (JNK-3) signaling, and enhanced expression of the antifibrotic factor bone morphogenetic protein (BMP)-5. However, without TGF-β1, Lefty-1 had no effect on Smad3, JNK-3, and BMP-5 activation and fibroblast-myofibroblast transdifferentiation. These findings indicate that Lefty-1 may prevent fibroblast-myofibroblast transdifferentiation in part via modulations of Smad3, JNK-3, and BMP-5 activities in the TGF-β/BMP signaling pathway.

Fig1. Lefty-1 modulates TGF-β/BMP signaling pathway in NRK-49F cells. Real-time PCR further validated that these results are consistent with gene microarray findings.

Fig2. Lefty-1 modulates TGF-β/BMP signaling pathway in NRK-49F cells. Western blot analysis also validated these gene microarray findings.

Case study 2: Erfei Chen, 2018

Although the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC, KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated. In this study, the researchers aimed to identify novel markers for CRC.

The team performed exome analysis of sporadic colorectal cancer (sCRC) coding regions to screen loss of function (LoF) mutation genes, and carried out systems-level approaches to confirm top rank gene in this study. BMP5 immunohistochemistry was performed on tumor microarrays (TMAs). Western blots and immunofluorescence staining were probed with the following antibodies anti-BMP5. The wild type and mutant BMP5 expression vector were constructed for stable BMP5 overexpression and tumor formation. The result support a novel concept that the importance of BMP5 in sCRC. The tumor suppressor role of BMP5 highlights its crucial role in CRC initiation and development.

Fig3. miR-32, miR-92a, and miR-655 inhibit the protein levels of BMP5 in SW480 cells.

Fig4. E-cadherin protein level analysis after transfection of BMP5 WT vector or infection of BMP5 lentivirus in HT-29 and SW480 cells, as well as siRNA-mediated knockdown in SW480 cells.

BMP5 has several biochemical functions, for example, BMP receptor binding,cytokine activity,growth factor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by BMP5 itself. We selected most functions BMP5 had, and list some proteins which have the same functions with BMP5. You can find most of the proteins on our site.

BMP5 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with BMP5 here. Most of them are supplied by our site. Hope this information will be useful for your research of BMP5.