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Bone. 2016 Feb;83:141-148. doi: 10.1016/j.bone.2015.11.003. Epub 2015 Nov 5.

Joint dysfunction and functional decline in middle age myostatin null mice.

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Research Program in Men's Health, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
Section of Anatomic Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States.
Department of Medicine, Boston University School of Medicine, Boston, MA 02118, United States.


Since its discovery as a potent inhibitor for muscle development, myostatin has been actively pursued as a drug target for age- and disease-related muscle loss. However, potential adverse effects of long-term myostatin deficiency have not been thoroughly investigated. We report herein that male myostatin null mice (mstn(-/-)), in spite of their greater muscle mass compared to wild-type (wt) mice, displayed more significant functional decline from young (3-6months) to middle age (12-15months) than age-matched wt mice, measured as gripping strength and treadmill endurance. Mstn(-/-) mice displayed markedly restricted ankle mobility and degenerative changes of the ankle joints, including disorganization of bone, tendon and peri-articular connective tissue, as well as synovial thickening with inflammatory cell infiltration. Messenger RNA expression of several pro-osteogenic genes was higher in the Achilles tendon-bone insertion in mstn(-/-) mice than wt mice, even at the neonatal age. At middle age, higher plasma concentrations of growth factors characteristic of excessive bone remodeling were found in mstn(-/-) mice than wt controls. These data collectively indicate that myostatin may play an important role in maintaining ankle and wrist joint health, possibly through negative regulation of the pro-osteogenic WNT/BMP pathway.


Age; Ankle joint; Grip strength; Myostatin; Treadmill endurance

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