Kawada Shigeo, Harada Atsushi, Hashimoto Naohiro
Department of Regenerative Medicine, Institute, National Center for Geriatrics and Gerontology, Morioka, Oobu, Aichi, Japan.
Department of Orthopedic Surgery, Hospital, National Center for Geriatrics and Gerontology, Morioka, Oobu, Aichi, Japan.
PLoS One. 2017 Jul 17;12(7):e0181457. doi: 10.1371/journal.pone.0181457. eCollection 2017.
Alendronate, a nitrogen-containing bisphosphonate, is well established as a treatment for osteoporosis through regulation of osteoclast activity. Previously, the pharmacological effects of bisphosphonates on cells outside the bone environment have been considered irrelevant because bisphosphonates target bone. Here we show that administration of alendronate impairs muscle regeneration in mice after bone fracture. A series of injections of alendronate alone or bone fracture alone did not affect muscle regeneration induced by cold injury. In contrast, alendronate treatment plus bone fracture severely impaired the regeneration of muscle that closely contacts the bone fracture site after cold injury. After cold injury, M-cadherin-positive myogenic cells disappeared in the damaged muscle areas of mice receiving the combination of alendronate treatment and bone fracture. The present results suggest that the muscle regeneration capacity is impaired by bone fracture in mice receiving alendronate treatment. The present research on the pharmacological effects of alendronate on muscle regeneration will aid in understanding of the in vivo action of alendronate on skeletal muscles.
阿仑膦酸钠是一种含氮双膦酸盐，通过调节破骨细胞活性，作为骨质疏松症的治疗药物已被广泛认可。此前，由于双膦酸盐靶向骨骼，其对骨外环境细胞的药理作用被认为无关紧要。在此，我们表明，阿仑膦酸钠给药会损害小鼠骨折后的肌肉再生。单独一系列注射阿仑膦酸钠或单独骨折均不影响冷损伤诱导的肌肉再生。相反，阿仑膦酸钠治疗加骨折严重损害了冷损伤后与骨折部位紧密接触的肌肉的再生。冷损伤后，接受阿仑膦酸钠治疗与骨折联合处理的小鼠受损肌肉区域中，M-钙黏蛋白阳性的成肌细胞消失。目前的结果表明，接受阿仑膦酸钠治疗的小鼠中，骨折会损害肌肉再生能力。目前关于阿仑膦酸钠对肌肉再生药理作用的研究将有助于理解阿仑膦酸钠在骨骼肌上的体内作用。
