High fatty acid content in rabbit serum is responsible for the differentiation of osteoblasts into adipocyte-like cells
High fatty acid content in rabbit serum is responsible for the differentiation of osteoblasts into adipocyte-like cells
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DOI：
10.1359/jbmr.1998.13.1.96
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发表时间：
1998-01-01
影响因子：
6.2
通讯作者：
Schmidt, A
中科院分区：
文献类型：
--
作者：
Diascro, DD;Vogel, RL;Schmidt, A
成骨细胞和脂肪细胞起源于共同的间充质前体细胞，随着年龄的增长，骨髓中的骨祖细胞减少，而脂肪细胞增加。我们观察到兔血清（RS）诱导人骨肉瘤SaOS-2/B10和MG-63细胞系，大鼠ROS 17/2.8细胞，小鼠颅骨衍生的成骨细胞MB 1.8细胞的脂肪样分化，证明了油红O阳性脂质囊泡的积累和碱性磷酸酶表达的减少。SaOS-2/B10和MG-63细胞，而不是ROS17/2.8或MB1.8细胞，表达显著水平的过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）家族的成员，其参与脂肪细胞分化的控制。然而，ROS 17/2.8和MG-63细胞均表达显著水平的脂肪细胞选择性标记物aP2脂肪酸结合mRNA，其可通过RS进一步增加。这些细胞类型表达PPARdelta/NUC-1，但不表达PPARalpha，表明不表达PPARgamma或PPARalpha的细胞能够分化成脂肪细胞样细胞。COS细胞的转染实验表明，与胎牛血清（FBS）相比，RS富含刺激PPAR依赖性转录的试剂。刺激活性是乙酸乙酯提取的，并且在RS中比在FBS中丰富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，棕榈酸，油酸和亚油酸的混合物，激活PPARs并诱导ROS17/2.8和SaOS-2/B10细胞的脂肪细胞样分化。这些发现表明脂肪酸或其代谢产物可以启动成骨细胞向脂肪样细胞的转变。
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 PPAR gamma 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 PPAR delta/NUC-1 but not PPAR alpha, indicating that cells that do not express either PPAR gamma or PPAR alpha 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,vas 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.