Whittemore Lisa-Anne, Song Kening, Li Xiangping, Aghajanian Jane, Davies Monique, Girgenrath Stefan, Hill Jennifer J, Jalenak Mary, Kelley Pamela, Knight Andrea, Maylor Rich, O'Hara Denise, Pearson Adele, Quazi Amira, Ryerson Stephanie, Tan Xiang Yang, Tomkinson Kathleen N, Veldman Geertruida M, Widom Angela, Wright Jill F, Wudyka Steve, Zhao Liz, Wolfman Neil M
Musculoskeletal Sciences Department, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA.
Biochem Biophys Res Commun. 2003 Jan 24;300(4):965-71. doi: 10.1016/s0006-291x(02)02953-4.
A human therapeutic that specifically modulates skeletal muscle growth would potentially provide a benefit for a variety of conditions including sarcopenia, cachexia, and muscular dystrophy. Myostatin, a member of the TGF-beta family of growth factors, is a known negative regulator of muscle mass, as mice lacking the myostatin gene have increased muscle mass. Thus, an inhibitor of myostatin may be useful therapeutically as an anabolic agent for muscle. However, since myostatin is expressed in both developing and adult muscles, it is not clear whether it regulates muscle mass during development or in adults. In order to test the hypothesis that myostatin regulates muscle mass in adults, we generated an inhibitory antibody to myostatin and administered it to adult mice. Here we show that mice treated pharmacologically with an antibody to myostatin have increased skeletal muscle mass and increased grip strength. These data show for the first time that myostatin acts postnatally as a negative regulator of skeletal muscle growth and suggest that myostatin inhibitors could provide a therapeutic benefit in diseases for which muscle mass is limiting.
一种能够特异性调节骨骼肌生长的人体治疗药物可能会对多种病症有益,包括肌肉减少症、恶病质和肌肉萎缩症。肌生成抑制素是转化生长因子-β家族生长因子的成员之一,是已知的肌肉量负调节因子,因为缺乏肌生成抑制素基因的小鼠肌肉量增加。因此,肌生成抑制素抑制剂作为肌肉合成代谢药物在治疗上可能有用。然而,由于肌生成抑制素在发育中的肌肉和成年肌肉中均有表达,目前尚不清楚它是在发育过程中还是在成体中调节肌肉量。为了验证肌生成抑制素在成体中调节肌肉量的假说,我们制备了一种针对肌生成抑制素的抑制性抗体并将其给予成年小鼠。在此我们表明,用抗肌生成抑制素抗体进行药物处理的小鼠骨骼肌量增加且握力增强。这些数据首次表明,肌生成抑制素在出生后作为骨骼肌生长的负调节因子发挥作用,并提示肌生成抑制素抑制剂可能会对肌肉量受限的疾病提供治疗益处。