Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5889130 | Bone | 2016 | 29 Pages |
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 (mstnâ/â), in spite of their greater muscle mass compared to wild-type (wt) mice, displayed more significant functional decline from young (3-6Â months) to middle age (12-15Â months) than age-matched wt mice, measured as gripping strength and treadmill endurance. Mstnâ/â 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 mstnâ/â 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 mstnâ/â 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.
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Authors
Wen Guo, Andrew D. Miller, Karol Pencina, Siu Wong, Amanda Lee, Michael Yee, Gianluca Toraldo, Ravi Jasuja, Shalender Bhasin,