Diascro D D, Vogel R L, Johnson T E, Witherup K M, Pitzenberger S M, Rutledge S J, Prescott D J, Rodan G A, Schmidt A
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
J Bone Miner Res. 1998 Jan;13(1):96-106. doi: 10.1359/jbmr.1998.13.1.96.
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.
成骨细胞和脂肪细胞起源于共同的间充质前体细胞。随着年龄增长，骨祖细胞减少，同时骨髓中脂肪细胞增加。我们观察到兔血清（RS）可诱导人骨肉瘤SaOS-2/B10和MG-63细胞系、大鼠ROS17/2.8细胞以及小鼠颅骨来源的成骨细胞MB1.8细胞向脂肪样细胞分化，油红O阳性脂质小泡的积累以及碱性磷酸酶表达的降低证明了这一点。SaOS-2/B10和MG-63细胞均表达显著水平的PPARγ mRNA，但ROS17/2.8细胞和MB1.8细胞不表达，PPARγ是过氧化物酶体增殖物激活受体（PPAR）家族的成员，与脂肪细胞分化的调控有关。然而，ROS17/2.8和MG-63细胞均表达显著水平的脂肪细胞选择性标志物aP2脂肪酸结合mRNA，RS可使其进一步增加。这些细胞类型表达PPARδ/NUC-1但不表达PPARα，表明既不表达PPARγ也不表达PPARα的细胞能够分化为脂肪样细胞。COS细胞转染实验表明，与胎牛血清（FBS）相比，RS富含刺激PPAR依赖性转录的因子。刺激活性可被乙酸乙酯提取，且RS中的含量比FBS高35倍。纯化和分析表明该提取物的主要成分是游离脂肪酸。此外，相同的脂肪酸，即棕榈酸、油酸和亚油酸的混合物，可激活PPAR并诱导ROS17/2.8和SaOS-2/B10细胞向脂肪样细胞分化。这些发现表明脂肪酸或其代谢产物可引发从成骨细胞向脂肪样细胞的转变。
