Bone biology osteocytes

Fig. 9.4 Osteoblast secretion and matrix vesicle formation. The outer surface of all bones is covered by fibroblast-like cells that differentiate into pre-osteoblasts that secrete osteoid matrix to remodel the surface as necessary. The surface osteoblasts extend into the osteoid tissue by long processes that attach to osteocytes (fully differentiated, nondividing osteoblasts) within the bone. Changes in the environment may be sensed by the osteocytes, which transmit them as remodeling signals to the osteoblasts. The osteoid matrix is filled with many small membrane-covered matrix vesicles containing various amounts of precipitated basic calcium phosphate (white circles) (Modified from Fig. 22-52 in The Molecular Biology of the Cell. B. Alberts et al., 4th Ed. 2002. Garland Science, Taylor Francis Group, New York)...

Studies have shown that certain Wnt proteins interact with a family of proteins named frizzled that can function as either direct receptors for Wnt proteins or as a component of a Wnt receptor complex. Secreted frizzled related protein-1 (SFRP-1) is expressed in osteoblasts and osteocytes and has been identified as a Wnt antagonist. SFRP-1 knockout mice demonstrate increased bone formation, possibiy due to the observed decrease in osteoblast/osteocyte apoptosis. In an effort to identify modulators of SFRP-1, a series of indole sulfonamides A was designed based upon a hit identified by FITS. The syntheses and biological activity of these compounds will be described. 

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