Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria.
Biochem Biophys Res Commun. 2010 Nov 12;402(2):180-5. doi: 10.1016/j.bbrc.2010.08.022. Epub 2010 Aug 11.
Thyroid hormones (T3,T4) have a broad range of effects on bone, however, its role in determining the quality of bone matrix is poorly understood. In-vitro, the immortalized mouse osteoblast-like cell line MC3T3-E1 forms a tissue like structure, consisting of several cell layers, whose formation is affected by T3 significantly. In this culture system, we investigated the effects of T3 on cell multiplication, collagen synthesis, expression of genes related to the collagen cross-linking process and on the formation of cross-links. T3 compared to controls modulated cell multiplication, up-regulated collagen synthesis time and dose dependently, and stimulated protein synthesis. T3 increased mRNA expressions of procollagen-lysine-1,2-oxoglutarate 5-dioxygenase 2 (Plod2) and of lysyloxidase (Lox), both genes involved in post-translational modification of collagen. Moreover, it stimulated mRNA expression of bone morphogenetic protein 1 (Bmp1), the processing enzyme of the lysyloxidase-precursor and of procollagen. An increase in the collagen cross-link-ratio Pyr/deDHLNL indicates, that T3 modulated cross-link maturation in the MC3T3-E1 culture system. These results demonstrate that T3 directly regulates collagen synthesis and collagen cross-linking by up-regulating gene expression of the specific cross-link related enzymes, and underlines the importance of a well-balanced concentration of thyroid hormones for maintenance of bone quality.
甲状腺激素（T3、T4）对骨骼有广泛的影响，但它在决定骨基质质量方面的作用尚未完全清楚。在体外，永生化的小鼠成骨样细胞系 MC3T3-E1 形成了一种组织样结构，由多个细胞层组成，其形成受 T3 的显著影响。在这个培养系统中，我们研究了 T3 对细胞增殖、胶原合成、与胶原交联过程相关基因的表达以及交联形成的影响。与对照组相比，T3 可调节细胞增殖，时间和剂量依赖性地上调胶原合成，并刺激蛋白质合成。T3 增加了前胶原赖氨酸-1,2-酮戊二酸 5-双加氧酶 2（Plod2）和赖氨酰氧化酶（Lox）的 mRNA 表达，这两种基因都参与胶原的翻译后修饰。此外，它还刺激骨形态发生蛋白 1（Bmp1）的 mRNA 表达，骨形态发生蛋白 1 是赖氨酰氧化酶前体和前胶原的加工酶。胶原交联比 Pyr/deDHLNL 的增加表明，T3 在 MC3T3-E1 培养系统中调节了胶原交联的成熟。这些结果表明，T3 通过上调特定交联相关酶的基因表达直接调节胶原合成和胶原交联，并强调了甲状腺激素平衡浓度对维持骨质量的重要性。
