BMP5

BMP5 Full Name

bone morphogenetic protein 5

BMP5 Introduction

BMP5 belongs to the bone morphogenetic protein branch of the TGF-beta superfamily and was among the first BMPs purified from demineralised bone on the basis of its ability to induce ectopic cartilage and bone formation. The human locus sits at 6p12.1, and the gene is transcribed as a precursor that is dimerised, cleaved by furin-type proteases and secreted as a mature disulphide-linked homodimer. Unlike BMP2 and BMP4, which are broadly expressed, BMP5 shows a more restricted distribution: it is prominent in developing skeletal elements, in the lung mesenchyme and in the adrenal cortex, and its transcription is controlled by a distal enhancer that responds to both retinoic acid and mechanical load.

Figure 1. BMP5 gene: function,pathway,and clinical significance.

Chondrocyte Commitment and Skeletal Patterning
In the developing limb, BMP5 is detected in the condensing mesenchyme just before chondrogenesis and later in the perichondrium, where it cooperates with BMP7 to drive Smad1/5/8 phosphorylation and the expression of Sox9 target genes. Loss of BMP5 alone produces only mild skeletal abnormalities, but compound deletion with BMP7 causes severe shortening of long bones, indicating that these ligands act redundantly to sustain chondrocyte proliferation. In the adult growth plate, BMP5 is re-expressed in the hypertrophic zone, and its level correlates with the rate of endochondral ossification; transgenic overexpression in cartilage accelerates ossification and increases bone mineral density.

Osteoarthritis, Fibrosis and Tumour Stroma
BMP5 is consistently downregulated in osteoarthritic cartilage, and a polymorphism in its promoter has been associated with knee osteoarthritis in several cohorts, suggesting that loss of anabolic BMP signalling contributes to matrix depletion. Conversely, in fibrotic disorders of lung and liver, BMP5 is induced in myofibroblasts and enhances collagen gel contraction in vitro. In colorectal and pancreatic carcinoma, BMP5 expression in the tumour stroma is linked to a desmoplastic, poorly vascularised phenotype and to resistance to chemotherapy, which has prompted interest in BMP antagonists such as noggin and gremlin as adjuncts to conventional treatment.

Alternate Names for BMP5

BMP5; bone morphogenetic protein 5; BMP-5; MGC34244;