Bone is a dynamic tissue which continually undergoes the processes of formation and resorption. It is, in fact, the sum of these processes which dictates net skeletal mass and the gross architecture of bone. Hence, any imbalance favoring the activities of bone resorbing over bone forming cells results in skeletal demineralization. It is therefore a truism that any major insights into the prevention of either generalized osteoporosis or focal bone loss such as occurs in periodontitis, rests on an understanding of the manner in which bone cells function. This application is aimed at investigating the activities of osteoclasts, the principal and perhaps exclusive resorptive cells of bone. These multinucleated giant cells which are specialized to degrade bone and cartilage have, until recently, been studied using multicellular assay systems such as bone rudiments in organ culture. Because of cellular heterogeneity, it was very difficult using such models to precisely identify the activity of any type of cell, in this case the osteoclast, and attribute to it a specific physiological event. Consequently, relatively little was known about the mechanisms by which these resorptive cells degrade bone matrix. Recently, however, methods for isolating and maintaining osteoclasts in culture have been developed and are presently extant in our laboratory. Moreover, we have used this technique to document that osteoclasts have the capacity to degrade bone collagen. It is, therefore, now possible for us to study the means by which bonafide osteoclasts degrade the organic matrix of bone and respond to calcitropic hormones. Specifically, we intend to: 1) determine the enzymatic means and physical optima of organic matrix degradation by osteoclasts 2) determine which """"""""bone-seeking"""""""" hormones interact directly with osteoclasts to alter their capacity to degrade collagen, and 3) identify those hormones interacting with intermediary (modulating) cells, such as osteoblasts or lymphocytes, which in turn produce osteoclast-effecting agents.
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| Blair, H C; Schlesinger, P H; Ross, F P et al. (1993) Recent advances toward understanding osteoclast physiology. Clin Orthop Relat Res :7-22 |
| Carano, A; Schlesinger, P H; Athanasou, N A et al. (1993) Acid and base effects on avian osteoclast activity. Am J Physiol 264:C694-701 |
| Teti, A; Blair, H C; Teitelbaum, S L et al. (1989) Cytoplasmic pH regulation and chloride/bicarbonate exchange in avian osteoclasts. J Clin Invest 83:227-33 |
| Teti, A; Blair, H C; Schlesinger, P et al. (1989) Extracellular protons acidify osteoclasts, reduce cytosolic calcium, and promote expression of cell-matrix attachment structures. J Clin Invest 84:773-80 |
| Lundy, M W; Lau, K H; Blair, H C et al. (1988) Chick osteoblasts contain fluoride-sensitive acid phosphatase activity. J Histochem Cytochem 36:1175-80 |
