MECHANICAL STRAIN-INDUCED NO PRODUCTION BY BONE-CELLS - A POSSIBLE ROLE IN ADAPTIVE BONE (RE)MODELING

The structural competence of the skeleton is maintained by an adaptive mechanism in which resident bone cells respond to load-induced strain s. To investigate the possible role of the messenger molecule nitric o xide (NO) in this response, we studied NO production in well-character ized organ culture systems, rat long bone-derived osteoblast-like (LOB s) cells, and embryonic chick osteocytes (LOCYs) in monolayer culture. In superfused cancellous bone cores, loading (for 15 min) produces in creases in NO2- (stable NO metabolite) release during the loading peri od, which paralleled those in PGI(2) and PGE(2). Loading of rat verteb rae and ulnae produces increases in NO2- release, and in ulnae NO synt hase inhibitors diminish these responses. Transient rapid increases in NO release are stimulated by strain hi both LOBs and LOCYs. Polymeras e chain reaction amplification of extracted mRNA shows that rat ulnae, LOBs, and LOCYs express both the inducible anti neuronal (constitutiv e) isoforms of NO synthase. Adaptability to mechanical strain relies o il assessment of the strain environment followed by modification of bo ne architecture. Immediate increases in NO production induced by loadi ng suggest the involvement of NO in strain measurement and cellular co mmunication to establish strain distribution, as well as potentially i n adaptive changes in bone cell behavior.