Kannikar Wongdee, Narattaphol Charoenphandhu, Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
World J Diabetes. 2015 Jun 10;6(5):673-8. doi: 10.4239/wjd.v6.i5.673.
It was previously understood that body weight gain and obesity observed in type 2 diabetes mellitus (T2DM) could be beneficial since body weight increase elevated bone mineral density and thus helped maintain the skeletal framework. However, a number of recent findings in humans and rodents have revealed that T2DM is not only associated with trabecular defects but also increases cortical porosity, and compromised bone cell function and bone mechanical properties. Hyperglycemia and insulin resistance in T2DM may further induce osteoblast apoptosis and uncoupling bone turnover. Prolonged accumulation of advanced glycation end products and diminished activity of lysyl oxidase, an essential enzyme for collagen cross-link, can lead to structural abnormalities of bone collagen fibrils, brittle matrix, and fragility fractures. Our studies in T2DM rats showed that dyslipidemia, which often occurs in T2DM, could obscure the T2DM-associated changes in bone microstructure and osteopenia. Longitudinal bone growth regulated by the growth plate chondrocytes is also impaired by T2DM since differentiation of growth plate chondrocytes is arrested and retained in the resting state while only a small number of cells undergo hypertrophic differentiation. Such a delayed chondrocyte differentiation may have also resulted from premature apoptosis of the growth plate chondrocytes. Nevertheless, the underlying cellular and molecular mechanisms of insulin resistance in osteoblasts, osteoclasts, osteocytes, and growth plate chondrocytes remain to be investigated.
先前人们认为，2 型糖尿病（T2DM）患者体重增加和肥胖是有益的，因为体重增加会提高骨密度，从而有助于维持骨骼结构。然而，人类和啮齿动物的一些最新发现表明，T2DM 不仅与骨小梁缺陷有关，还会增加皮质孔隙率，损害骨细胞功能和骨力学性能。T2DM 中的高血糖和胰岛素抵抗可能进一步诱导成骨细胞凋亡和骨转换脱耦联。糖基化终末产物的长期积累和赖氨酰氧化酶活性的降低，会导致骨胶原纤维的结构异常、脆弱的基质和脆性骨折。我们在 T2DM 大鼠中的研究表明，T2DM 中常发生的血脂异常可能掩盖 T2DM 相关的骨微结构变化和骨质疏松症。T2DM 也会损害由生长板软骨细胞调节的纵向骨生长，因为生长板软骨细胞的分化被阻滞并保持在静止状态，而只有少数细胞经历肥大分化。这种软骨细胞分化延迟可能也源于生长板软骨细胞的过早凋亡。然而，成骨细胞、破骨细胞、骨细胞和生长板软骨细胞中胰岛素抵抗的潜在细胞和分子机制仍有待研究。
