Internal Medicine 1, Shimane University Faculty of Medicine, Izumo, Japan.
Department of Laboratory Medicine, Shimane University Faculty of Medicine, Izumo, Japan.
Biochem Biophys Res Commun. 2014 Jul 18;450(1):482-7. doi: 10.1016/j.bbrc.2014.05.145. Epub 2014 Jun 9.
Vitamin D deficiency and advanced glycation end products (AGEs) are suggested to be involved in the pathogenesis of osteoporosis and sarcopenia. However, the effects of vitamin D and AGEs on myogenesis and the interaction between muscle and bone remains still unclear. We previously showed that osteoglycin (OGN) is secreted from myoblasts and stimulates osteoblastic differentiation, suggesting that it plays important roles in the interaction between muscle and bone. The aim of this study is thus to examine the effects of vitamin D and AGEs on myoblastic differentiation of C2C12 cells and osteoblastic differentiation of osteoblastic MC3T3-E1 cells through OGN expression. 1α,25-dihydroxyvitamin D3 (1,25D) and eldecalcitol, an active vitamin D analog, induced the expression of MyoD, myogenin and OGN, and these effects were abolished by vitamin D receptor (VDR) suppression by siRNA in C2C12 cells. Moreover, conditioned medium from 1,25D-pretreated C2C12 cells stimulated the expression of type 1 collagen and alkaline phosphatase in MC3T3-E1 cells, compared to control medium from 1,25D-untreated C2C12 cells. In contrast, conditioned medium from VDR-suppressed and 1,25D-pretreated C2C12 cells showed no effects. AGE2 and AGE3 suppressed the expression of MyoD, myogenin and OGN in C2C12 cells. Moreover, 1,25D blunted the AGEs' effects. In conclusion, these findings showed for the first time that active vitamin D plays important roles in myogenesis and muscle-induced osteoblastogenesis through OGN expression. Active vitamin D treatment may rescue the AGEs-induced sarcopenia as well as - suppressed osteoblastic differentiation via OGN expression in myoblasts.
维生素 D 缺乏和晚期糖基化终产物（AGEs）被认为与骨质疏松症和肌肉减少症的发病机制有关。然而，维生素 D 和 AGEs 对成肌细胞的影响以及肌肉和骨骼之间的相互作用仍然不清楚。我们之前表明，骨连蛋白（OGN）由成肌细胞分泌并刺激成骨细胞分化，表明它在肌肉和骨骼之间的相互作用中发挥重要作用。因此，本研究旨在通过 OGN 表达来研究维生素 D 和 AGEs 对 C2C12 细胞的成肌分化和成骨细胞 MC3T3-E1 细胞的成骨分化的影响。1α，25-二羟维生素 D3（1,25D）和艾地骨化醇，一种活性维生素 D 类似物，诱导 MyoD、myogenin 和 OGN 的表达，并且这些作用在 C2C12 细胞中通过 siRNA 抑制维生素 D 受体（VDR）而被消除。此外，与未用 1,25D 处理的 C2C12 细胞的对照培养基相比，用 1,25D 预处理的 C2C12 细胞的条件培养基刺激 MC3T3-E1 细胞中 1 型胶原和碱性磷酸酶的表达。相比之下，用 VDR 抑制和 1,25D 预处理的 C2C12 细胞的条件培养基没有作用。AGE2 和 AGE3 抑制 C2C12 细胞中 MyoD、myogenin 和 OGN 的表达。此外，1,25D 减弱了 AGEs 的作用。总之，这些发现首次表明活性维生素 D 通过 OGN 表达在成肌细胞和肌肉诱导的成骨细胞中发挥重要作用。通过在成肌细胞中表达 OGN，活性维生素 D 治疗可能通过 AGEs 诱导的肌肉减少症以及抑制的成骨细胞分化来挽救。
