Rapamycin could increase the effects of melatonin against age-dependent bone loss
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Gerontologie+Geriatrie Original Contributions Z Gerontol Geriat https://doi.org/10.1007/s00391-019-01659-4 Received: 30 May 2019 Accepted: 5 November 2019 © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019
Zhou-Shan Tao1 · Han-Li Lu1 · Neng-Feng Ma1 · Rou-Tian Zhang1 · Yang Li1 · Min Yang1 · Hong-Guang Xu2 1
Department of Trauma Orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, China 2 Spine Research Center of Wannan Medical College; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution; Dept of Spine Surgery, Yijishan hospital of Wannan Medical College, Wuhu, China
Rapamycin could increase the effects of melatonin against agedependent bone loss Introduction The prevalence of senile osteoporosis increases progressively with aging of the world population and the osteoporotic fractures among old people has become a major public health problem since its association with high medical costs, considerable disability, and an increased risk of mortality [1, 2]. People who often suffer from osteoporosis are more likely to suffer from bone fractures. Therefore, emphasis should be given to the investigation of better treatment for suppressing excessive bone resorption using effective and safe strategies. Current drugs for the prevention and treatment of osteoporosis include estrogen, selective estrogen receptor modulators, calcitonin, and bisphosphonates but sometimes have adverse effects, such as atypical femoral fractures, jaw necrosis and breast cancer [3–5]. Therefore, there is a need to develop new treatments to prevent and treat osteoporosis. Melatonin (MEL) is N-acetyl-5methoxy-tryptamine. It is a hormone that is synthesized principally in the pineal gland and other organs and influences circadian and circannual rhythms as well as sleep in many ways [6]. It is also an antioxidant that reduces oxidative stress in several ways by direct detoxification of reactive oxygen and reactive nitrogen species, and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes [7, 8]. Systemic administration
of MEL had been previously documented to stimulate bone fracture repair and to increase bone mass [9]. In addition, MEL may also be an effective hormone in the treatment of bone changes in estrogen deficiency states [10]. Recently, researchers have pointed out the important role of autophagy in maintenance of bone homeostasis [11]. Rapamycin (RAP), as an immunosuppressive drug, has been widely used to treat the rejection after organ transplantation for many years. Besides, RAP has been confirmed to have the pharmacological effect of inducing autophagy by inhibition of mammalian target of rapamycin (mTOR), an important suppressor of autophagy [12]. Luo et al. demonstrated that pharmacological activation of autophagy by RAP can increase bone mineral density (BMD) and improve bone microstructure in a senile male rat osteoporosis model [13]. It has been reported that MEL could enhance bone formation and
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