Bone morphogenetic proteins and skeletal development: the kidney-bone connection
The bone morphogenetic proteins (BMPs) are a family of pleiotropic morphogens isolated and cloned from the demineralized extracellular matrix of bone. BMPs and related cartilage-derived morphogenetic proteins (CDMPs) initiate, promote and maintain bone and cartilage. The pleiotropic effects of BMPs are based on concentration-dependent thresholds. Targeted disruption of gene action by homologous recombination has demonstrated the role of BMP 7 in kidney, eye and skeletal development. BMP 7 is critical for kidney tubulogenesis, retinal pigmented epithelium differentiation and skeletal pattern. BMP 7 is also synthesized by the kidney and is detectable in serum; hence BMP 7 is both an autocrine and endocrine morphogen. It is likely renal BMP 7 may influence skeletal development and growth in children although there may be sources of other BMPs with skeletogenic actions. In conclusion, we are beginning to unravel the mysteries of kidney-bone connection with special reference to pediatric nephrology.