ARACHIDONIC-ACID METABOLISM BY ADULT HUMAN OSTEOBLAST-LIKE CELLS EXHIBITS SEXUALLY DIMORPHIC CHARACTERISTICS

The eicosanoids, including prostaglandin E-2 (PGE(2)) and other bioact ive arachidonic acid metabolites, are important local mediators of bon e remodeling. Presumably, the limited or excessive synthesis of the ei cosanoids could compromise bone homeostasis. We have noted that the st imulated release of arachidonic acid by adult male donor derived human osteoblast-like (hOB) cells exceeded the stimulated release measured for female-derived hOB cells by 1.5-fold. Assays of PGE(2) biosynthesi s by cytokine-stimulated hOB cells also demonstrated a sex-linked diff erence, such that male hOB cell PGE(2) production exceeded female cell production by 1.6-2.2-fold. The calcium-dependent cytoplasmic phospho lipase A(2) activity in subcellular fractions prepared from hOB cell h omogenates was higher in both the cytosolic (1.6-fold) and particulate (1.5-fold) fractions from the male cells than in those prepared from f emale hOB cells, suggesting a molecular basis for the observed sexuall y dimorphic characteristics related to arachidonic acid metabolism by hOB cells. The relatively limited capacity of the female cells may lim it needed intracellular and intercellular signaling during bone remode ling, thereby contributing to the development of bone pathology. (C) 1 998 Wiley-Liss, Inc.