Arachidonic acid metabolism by adult human osteoblast-like cells exhibits sexually dimorphic characteristics

Abstract

The eicosanoids, including prostaglandin E2 (PGE2) and other bioactive arachidonic acid metabolites, are important local mediators of bone remodeling. Presumably, the limited or excessive synthesis of the eicosanoids could compromise bone homeostasis. We have noted that the stimulated 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 PGE2 biosynthesis by cytokine-stimulated hOB cells also demonstrated a sex-linked difference, such that male hOB cell PGE2 production exceeded female cell production by 1.6-2.2-fold. The calcium-dependent cytoplasmic phospholipase A2 activity in subcellular fractions prepared from hOB cell homogenates was higher in both the cytosolic (1.6-fold) and particulate (1.5-fold) fractions from the male cells than in those prepared from female hOB cells, suggesting a molecular basis for the observed sexually dimorphic characteristics related to arachidonic acid metabolism by hOB cells. The relatively limited capacity of the female cells may limit needed intracellular and intercellular signaling during bone remodeling, thereby contributing to the development of bone pathology.

Unmasking Sex-Based Disparity in Neuronal Metabolism

“…Pharmacological inhibition of cPLA2 in neurons from females decreased starvationinduced lipid droplet formation and cellular respiration to levels that were similar to those seen in males, thus negating the sex-based survival advantage. This sex-based finding in stressed rodent neurons is in contrast to human osteoblast-like cells under baseline conditions, where cPLA2 activity is higher in cells from males compared with females [58]. It is worthy to note that at baseline, the number of lipid droplets and concentration of triglycerides was similar between neurons from males and females, whereas the concentration of FFA was higher in neurons from males; and that treatment with L-carnitine increased cellular respiration and improved survival in neurons from males, pointing to a reduced capacity, or proclivity, to utilize FFA in males [48].…”

Estrogen Potentiates the Combined Effects of Transforming Growth Factor-β and Tumor Necrosis Factor-α on Adult Human Osteoblast-like Cell Prostaglandin E2 Biosynthesis

“…1A, B). Because arachidonic acid metabolism by female hOB cells and male hOB cells exhibits sexually dimorphic characteristics [25], the responses of the cells of each sex were assessed independently in this experiment. The application of TGFβ, TNF, or both cytokines simultaneously significantly stimulated hOB cell PGE 2 production (p ≤ 0.01), agreeing with previous observations [12].…”