Olsson Karl, Saini Amarjit, Strömberg Anna, Alam Seher, Lilja Mats, Rullman Eric, Gustafsson Thomas
Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
Endocrinology. 2016 Jan;157(1):98-111. doi: 10.1210/en.2015-1685. Epub 2015 Oct 15.
Presence of the vitamin D receptor and direct effects of vitamin D on the proliferation and differentiation of muscle precursor cells have been demonstrated in animal models. However, the effects and mechanisms of vitamin D actions in human skeletal muscle, and the presence of the vitamin D receptor in human adult skeletal muscle, remain to be established. Here, we investigated the role of vitamin D in human muscle cells at various stages of differentiation. We demonstrate that the components of the vitamin D-endocrine system are readily detected in human muscle precursor cells but are low to nondetectable in adult skeletal muscle and that human muscle cells lack the ability to convert the inactive vitamin D-metabolite 25-hydroxy-vitamin D3 to the active 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3). In addition, we show that 1α,25(OH)2D3 inhibits myoblast proliferation and differentiation by altering the expression of cell cycle regulators and myogenic regulatory factors, with associated changes in forkhead box O3 and Notch signaling pathways. The present data add novel information regarding the direct effects of vitamin D in human skeletal muscle and provide functional and mechanistic insight to the regulation of myoblast cell fate decisions by 1α,25(OH)2D3.
在动物模型中已证实存在维生素D受体以及维生素D对肌肉前体细胞增殖和分化的直接影响。然而，维生素D在人类骨骼肌中的作用及机制，以及维生素D受体在成人骨骼肌中的存在情况，仍有待确定。在此，我们研究了维生素D在人类肌肉细胞不同分化阶段的作用。我们证明，维生素D内分泌系统的成分在人类肌肉前体细胞中易于检测到，但在成人骨骼肌中含量较低或无法检测到，并且人类肌肉细胞缺乏将无活性的维生素D代谢物25-羟基维生素D3转化为活性1α,25-二羟基维生素D3（1α,25(OH)2D3）的能力。此外，我们表明1α,25(OH)2D3通过改变细胞周期调节因子和成肌调节因子的表达来抑制成肌细胞的增殖和分化，同时叉头框O3和Notch信号通路也会发生相关变化。目前的数据为维生素D对人类骨骼肌的直接影响增添了新信息，并为1α,25(OH)2D3调节成肌细胞命运决定提供了功能和机制方面的见解。
