Osteoprotegrin (OPG) as a therapeutic target to combat age associated muscle loss.

背景：骨质保护素（OPG）是一种循环因子，通常与骨吸收调节有关。OPG作为RANK分子配体（RANKL）的诱饵受体。RANKL与OPG的比例必须保持平衡，以维持骨转换（Grimaud等，2003；Kong等，1999；Lacey等，1998）；当RANKL水平升高时，OPG被释放，确保当RANK/RANKL结合时骨吸收不会持续发生。在小鼠退行性疾病模型中，OPG也从肌肉中释放。然而，导致这些变化的具体途径尚未确定（Shen等人，2017；Dufresne等人，2016a； Dufresne等人，2016b； Dufresne等人，2015）。骨保护素对衰老的影响50岁以后，肌肉质量以每年1-2%的速度下降，在50 - 75岁之间，肌肉质量总下降约25% （Delmonico et al., 2009; Marcell, 2003; LaPier, 1997; Waters et al., 2008）。肌少症的最新定义包括三个关键参数；肌肉力量、肌肉质量/数量和体能水平低。肌肉质量和数量是可能的肌肉减少症的主要指标（Cruz-Jentoft et al., 2018）。早期诊断和治疗肌肉减少症对于减轻因不及时治疗而带来的个人、社会和经济负担至关重要（Cruz-Jentoft et al., 2018）。

BackgroundOsteoprotegerin (OPG) is a circulating factor more commonly associated with the regulation of bone resorption. OPG acts as a decoy receptor to the ligand of the RANK molecule (RANKL). The proportion of RANKL to OPG must remain balanced to maintain bone turnover (Grimaud et al., 2003 Kong et al., 1999; Lacey et al., 1998); OPG is released when RANKL levels are elevated, ensuring bone resorption does not continually occur when RANK/RANKL are bound. OPG is also released from muscle in murine models of degenerative diseases. However, the specific pathway that causes these changes has not been identified (Shen et al., 2017; Dufresne et al., 2016a; Dufresne et al., 2016b; Dufresne et al., 2015). The Impact of Osteoprotegerin in AgeingAfter the age of 50 years old, muscle mass declines by 1-2% per year, with a total decline of ~25% between the ages of 50 and 75 years (Delmonico et al., 2009; Marcell, 2003; LaPier, 1997; Waters et al., 2008). The most recent definition of sarcopenia includes three key parameters; low levels of muscle strength, muscle quality/quantity and physical performance. Muscle quality and quantity are the primary indicators of probable sarcopenia (Cruz-Jentoft et al., 2018). Early diagnosis and treatment of sarcopenia is essential to mitigate the high personal, social and economic burdens that it becomes associated with when left untreated (Cruz-Jentoft et al., 2018).