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 precursors. With aging, there is a decrease in osteoprogenitor cells that parallels an increase of adipocytes in bone marrow. We observed that rabbit serum (RS) induces adipocyte-like differentiation in human osteosarcoma SaOS-2/B10 and MG-63 cell lines, in rat ROS17/2.8 cells, and in mouse calvaria-derived osteoblastic MB1.8 cells, as evidenced by the accumulation of Oil Red O positive lipid vesicles and the decrease in alkaline phosphatase expression. Both SaOS-2/B10 and MG-63 cells, but not ROS17/2.8 nor MB1.8 cells, express significant levels of PPARgamma mRNA, a member of the peroxisome proliferator activated receptor (PPAR) family that has been implicated in the control of adipocyte differentiation. However, both ROS17/2.8 and MG-63 cells express significant levels of the adipocyte selective marker, aP2 fatty acid binding mRNA, which can be further increased by RS. These cell types express PPARdelta/NUC-1 but not PPARalpha, indicating that cells that do not express either PPARgamma or PPARalpha are capable of differentiating into adipocyte-like cells. Transfection experiments in COS cells showed that compared with fetal bovine serum (FBS), RS is rich in agents that stimulate PPAR-dependent transcription. The stimulatory activity was ethyl acetate extractable and was 35-fold more abundant in RS than in FBS. Purification and analysis revealed that the major components of this extract are free fatty acids. Furthermore, the same fatty acids, a mixture of palmitic, oleic, and linoleic acids, activate the PPARs and induce adipocyte-like differentiation of both ROS17/2.8 and SaOS-2/B10 cells. These findings suggest that fatty acids or their metabolites can initiate the switch from osteoblasts to adipocyte-like cells.
Diascro
D D
DD
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Vogel
R L
RL
Johnson
T E
TE
Witherup
K M
KM
Pitzenberger
S M
SM
Rutledge
S J
SJ
Prescott
D J
DJ
Rodan
G A
GA
Schmidt
A
A
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005227:Fatty Acids / Q000097:blood* / Q000302:isolation & purification / Q000502:physiology; D005312:Fetal Blood / Q000502:physiology; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D005227:Fatty Acids; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors