title: Joint dysfunction and functional decline in middle age myostatin null mice.
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.
authors.affiliation: 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.
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.affiliation: Section of Anatomic Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.affiliation: 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.
authors.forename: Karol
authors.initials: K
authors.lastname: Pencina
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: Siu
authors.initials: S
authors.lastname: Wong
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Yee
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, United States.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Toraldo
authors.affiliation: 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.
authors.forename: Ravi
authors.initials: R
authors.lastname: Jasuja
authors.affiliation: 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.
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling; D005121:Extremities / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation; D006984:Hypertrophy; D007596:Joints / Q000473:pathology* / Q000503:physiopathology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009132:Muscles / Q000473:pathology; D055435:Myostatin / Q000172:deficiency* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013710:Tendons / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; C525912:Mstn protein, mouse; D055435:Myostatin; D012333:RNA, Messenger
keywords: Age; Ankle joint; Grip strength; Myostatin; Treadmill endurance