Study Clarifies Inhibition of Osteoblast Maturation
August 26, 2005
As you read this sentence, your body is fast at work forming new bone through a dynamic biological process that centers on the osteoblast. This unique cell possesses the ability to lay down a supportive, lattice-like organic matrix that later mineralizes into bone. Scientists have known for years that osteoblasts are the direct offspring of adult progenitor cells that reside en masse in the bone marrow. Depending on the specific biochemical prompt that reaches them, these adult precursor cells can produce not only osteoblasts but fat and muscle producing cells. This variability has led bone researchers not only to try and determine the molecular signals that specify for osteoblasts, but also the equally intriguing question: Which biochemical factors inhibit the maturation of developing osteoblasts? One answer is transforming growth factor-beta (TGF-beta), which is secreted by mature osteoblasts into the nearby extracellular matrix, or within the general vicinity of developing osteoblasts. NIDCR grantees reported a few years ago that TGF-beta puts the brakes on osteoblast differentiation by repressing a gene-activating protein, or transcription factor, called Runx2. They also showed that TGF-beta does so by activating a central regulatory mechanism that runs through the protein Smad3. Exactly how Smad3 repressed Runx2 remained unclear, however, leaving a key informational gap in learning to control or manipulate this process in people with bone disorders. Now, as reported in the July 20 issue of the European Molecular Biology Organization (EMBO) Journal, these same grantees describe the process in greater detail.