BMP-Mediated Metabolic Shifts Are Associated With Mesenchymal Cell Differentiation

Background: Disorders of mesenchymal tissues such as osteoarthritis have been associated with changes in energy metabolism. Bone Morphogenetic Proteins (BMPs) are signalling proteins controlling mesenchymal cell differentiation and their involvement in energy metabolism has become a major point of interest. Here, we compared the action of BMPs in three mesenchymal tissues: adipose, cartilage, and bone.

Hypothesis: Specific BMPs regulate discrete but common aspects of energy metabolism in all mesenchymal lineages.

Methods and Results: We conducted a scoping review on the role of BMPs in adipose tissue, cartilage, and bone. Searching for “bmp metabolism” and “adipocyte”, “chondrocyte”, or “osteoblast”, we identified 13, 34, and 80 articles respectively. Commonalities were found between BMP-dependent adipocyte and chondrocyte differentiation. BMP2 was associated with increased glycolysis, whereas BMP7 increased oxidative phosphorylation in both chondrocytes and adipocytes. Although there is some evidence that BMPs regulate energy metabolism in osteoblasts, details remained unclear partially due to the heterogeneity of bone tissue. Relating this with our lab results, we compared cartilage from the temporomandibular joint (TMJ) of BMP7-deficient or control mice. A quantitative proteomics screen identified changes to mitochondrial energy metabolism. Indeed, the downregulation of Cox5a and UCP1 in 2- and 4-week-old BMP7-deficient TMJ cartilage was confirmed by immunohistochemistry.

Conclusion: Literature evidence suggests conserved roles of BMPs in the regulation of energy metabolism in different mesenchymal cell types. BMP7 induces similar shifts in metabolic function in chondrocytes and adipocytes. Thus, BMP signalling plays a critical role in mediating differences in energy metabolism associated with functional properties of cartilage and bone.