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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.

Author information

1
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.
2
Section of Anatomic Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States.
3
Department of Medicine, Boston University School of Medicine, Boston, MA 02118, United States.

Abstract

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.

KEYWORDS:

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

PMID:
26549246
PMCID:
PMC5461924
DOI:
10.1016/j.bone.2015.11.003
[Indexed for MEDLINE]
Free PMC Article

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