HIGH FATTY-ACID CONTENT IN RABBIT SERUM IS RESPONSIBLE FOR THE DIFFERENTIATION OF OSTEOBLASTS INTO ADIPOCYTE-LIKE CELLS

Osteoblasts and adipocytes originate from common mesenchymal precursor s, With aging, there is a decrease in osteoprogenitor cells that paral lels an increase of adipocytes in bone marrow. We observed that rabbit serum (RS) induces adipocyte-like differentiation in human osteosarco ma SaOS-2/B10 and MG-63 cell lines, in rat ROS17/2.8 cells, and in mou se calvaria-derived osteoblastic MB1.8 cells, as evidenced by the accu mulation of Oil Red O positive lipid vesicles and the decrease in alka line phosphatase expression. Both SaOS-2/B10 and MG-63 cells, but not ROS17/2.8 nor MB1.8 cells, express significant levels of PPAR gamma mR NA, a member of the peroxisome proliferator activated receptor (PPAR) family that has been implicated in the control of adipocyte differenti ation. However, both ROS17/2.8 and MG-63 cells express significant lev els of the adipocyte selective marker, aP2 fatty acid binding mRNA, wh ich can be further increased by RS. These cell types express PPAR delt a/NUC-1 but not PPAR alpha, indicating that cells that do not express either PPAR gamma or PPAR alpha are capable of differentiating into ad ipocyte-like cells. Transfection experiments in COS cells showed that compared with fetal bovine serum (FBS), RS is rich in agents that stim ulate PPAR-dependent transcription. The stimulatory activity was ethyl acetate extractable and,vas 35-fold more abundant in RS than in FBS, Purification and analysis revealed that the major components of this e xtract are free fatty acids. Furthermore, the same fatty acids, a mixt ure of palmitic, oleic, and linoleic acids, activate the PPARs and ind uce adipocyte-like differentiation of both ROS17/2.8 and SaOS-2/B10 ce lls. These findings suggest that fatty acids or their metabolites can initiate the switch from osteoblasts to adipocyte-like cells.