Transforming growth factor β2 inhibits adipocyte differentiation induced by skeletal unloading in rat bone marrow stroma
Transforming growth factor β2 inhibits adipocyte differentiation induced by skeletal unloading in rat bone marrow stroma
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DOI：
10.1359/jbmr.2002.17.4.668
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发表时间：
2002-04-01
影响因子：
6.2
通讯作者：
Marie, PJ
中科院分区：
文献类型：
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作者：
Ahdjoudj, S;Lasmoles, F;Marie, PJ
大鼠后肢悬浮诱导的骨骼卸载减少了骨形成并引起骨质减少，但其对脂肪生成的影响尚不清楚。我们评估了卸载和转化生长因子（TGF）β2 对骨髓基质细胞脂肪细胞分化与成骨细胞分化的影响。骨骼快速卸载（4-7天）降低了成骨细胞转录因子Runx2、骨钙素（OC）和I型胶原信使RNA（mRNA）的水平，并减少了长骨干骺端的骨形成。相反，卸载第4天时，脂肪细胞转录因子过氧化物酶体增殖物激活受体γ2（PPARγ2）的表达增加，第7天时，骨髓基质中脂肪细胞分化基因脂蛋白脂肪酶（LPL）和aP2的表达增加。一致地，卸载增加了骨髓基质中脂肪细胞的数量和体积。连续（0-7天）和晚期（4-7天）TGF-β2治疗纠正了Cbfal/Runx2、OC和I型胶原mRNA的异常表达，并使无负载干骺端骨中的骨形成正常化。此外，两种TGF-β2治疗均在第4天时降低了PPARγ2和C/EBPα mRNA水平，并在第7天时使aP2和LPL表达以及脂肪细胞数量和体积正常化。这些结果表明，骨骼卸载增加脂肪细胞分化，同时抑制成骨细胞分化。这些异常可被 TGF-β2 预防和逆转，这表明 TGF-β 在控制骨髓基质的脂肪形成分化中发挥作用。
Skeletal unloading induced by hindlimb suspension in rats reduces bone formation and induces osteopenia, but its effect on adipogenesis is unknown. We assessed the effects of unloading and transforming growth factor (TGF) beta2 on bone marrow stromal cell adipocyte differentiation in relation with osteoblast differentiation. Skeletal unloading rapidly (4-7 days) decreased osteoblast transcription factor Runx2, osteocalcin (OC), and type I collagen messenger RNA (mRNA) levels and reduced bone formation in the long bone metaphysis. Conversely, unloading increased expression of the adipocyte transcription factor peroxisome proIiferatoractivated receptor gamma2 (PPARgamma2) at 4 days and increased expression of the adipocyte differentiation genes lipoprotein lipase (LPL) and aP2 in the bone marrow stroma at 7 days. Consistently, unloading increased the number and volume of adipocytes in the bone marrow stroma. Continuous (0-7 days) and late (4-7 days) treatments with TGF-beta2 corrected the abnormal expression of Cbfal/Runx2, OC, and type I collagen mRNAs and normalized bone formation in unloaded metaphyseal bone. Moreover, both TGF-beta2 treatments decreased PPARgamma2 and C/EBPalpha mRNA levels at 4 days and normalized aP2 and LPL expression and adipocyte number and volume at 7 days. These results show that skeletal unloading increases adipocyte differentiation concomitantly with inhibition of osteoblast differentiation. These abnormalities are prevented and reversed by TGF-beta2, suggesting a role for TGF-beta in the control of adipogenic differentiation in the bone marrow stroma.