What is BMP7 and What Does It Do in the Body?

Bone Morphogenetic Protein 7 (BMP7) is a protein belonging to the transforming growth factor-beta (TGF-β) superfamily. This family is involved in various cellular processes. BMP7 is a secreted ligand that plays a significant role in cell growth and differentiation, acting as a signaling molecule to direct cell fate and behavior.

BMP7’s Role in the Body

BMP7 performs several physiological functions, contributing to the development and maintenance of various tissues. It plays a role in kidney development, inducing the transformation of mesenchymal cells into the epithelial tissue that forms kidney tubules and glomeruli. In the adult kidney, BMP7 also helps maintain organ structure by inhibiting epithelial-mesenchymal transition, a process that can lead to fibrosis.

The protein is also a factor in bone formation and repair. It induces the formation of cartilage and bone, promoting the differentiation of mesenchymal stem cells into chondrocytes and osteoclasts. These cells are involved in bone and cartilage development and remodeling.

BMP7 contributes to calcium regulation and bone homeostasis. It is involved in healing bone fractures, promoting fracture healing and inducing ectopic bone formation. Beyond bone and kidney, BMP7 is expressed in other tissues during embryonic development, including the eyes, heart, limbs, and brain.

BMP7’s signaling pathways involve its binding to specific receptors on cell surfaces. This binding activates intracellular pathways, such as the phosphorylation of SMAD proteins, which then influence gene transcription. These actions contribute to tissue regeneration and repair across multiple organ systems.

BMP7 and Health Conditions

Dysregulation or deficiency of BMP7 can have implications for human health, contributing to the development or progression of specific conditions. In chronic kidney disease (CKD), reduced levels or activity of BMP7 are observed. This decrease can facilitate kidney damage progression, as the protein normally counteracts profibrotic effects and helps maintain kidney function.

The decline in BMP7 expression in the kidney, particularly in conditions like diabetic nephropathy, can lead to increased fibrosis and loss of nephron function. Studies show a negative correlation between serum BMP7 levels and indicators of kidney dysfunction, such as serum creatinine and blood phosphorus. A positive correlation is observed with estimated glomerular filtration rate (eGFR).

BMP7 is also related to bone disorders, especially those seen with kidney disease. In chronic kidney disease-mineral and bone disorder (CKD-MBD), lower BMP7 levels are associated with altered calcium and phosphorus metabolism. Reduced BMP7 is linked to the bone abnormalities observed in these patients.

Beyond kidney and bone, altered BMP7 activity is involved in other conditions. Its anti-inflammatory and anti-fibrotic properties suggest its dysregulation contributes to diseases with inflammation and tissue scarring. Reduced BMP7 expression has been linked to various diseases, including osteoporosis, cardiovascular disease, and diabetes.

BMP7 as a Therapeutic Agent

BMP7 is investigated and utilized as a therapeutic agent for medical conditions, particularly those involving tissue repair and regeneration. Recombinant human BMP7 (rhBMP7), also known as osteogenic protein-1 (OP-1), has seen clinical application, especially in orthopedic surgery. It promotes bone regeneration and enhances fracture healing in challenging situations like non-union fractures.

rhBMP7 can be applied in bone grafts to encourage new bone formation. Its use has been evaluated in various clinical conditions, including periprosthetic fracture treatment, osteotomies, and enhancing healing after acetabular reconstruction. Clinical trials demonstrate rhBMP7’s efficacy in bone healing.

Beyond bone repair, BMP7 shows promise in treating kidney diseases. Administering exogenous BMP7 has demonstrated protective effects in experimental models of acute and chronic kidney injuries. It counteracts profibrotic effects of other growth factors, reduces inflammation, and prevents kidney function loss by reversing processes like epithelial-to-mesenchymal transition.

Research explores BMP7’s potential in other fibrotic and inflammatory conditions affecting organs such as the liver, lung, and heart. The protein’s ability to modulate fibrogenesis and reduce proinflammatory molecules makes it a candidate for broader therapeutic applications.

Considerations for BMP7 Use

The therapeutic application of BMP7 involves several considerations, including optimal administration and potential side effects. Recombinant BMP7 proteins, small molecule agonists, and gene therapy techniques are being explored to enhance BMP7 activity. However, soluble recombinant human BMPs can have a short half-life due to rapid clearance and enzymatic degradation, which may necessitate higher doses or novel delivery systems.

Further research is needed to optimize BMP7 delivery methods for sustained and localized effects. While clinical use in bone repair has shown a favorable safety profile, understanding the full spectrum of potential side effects and long-term implications remains an area of ongoing study.

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