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Melatonin combined with treadmill exercise suppresses aberrant chondrocyte behavior in osteoarthritic cartilage via TGF‐β1 upregulation (LB834)
Author(s) -
Choi Jeonghyun,
Hong Yunkyung,
Hong Yonggeun
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb834
Subject(s) - melatonin , downregulation and upregulation , chondrocyte , cartilage , endocrinology , medicine , metalloproteinase , osteoarthritis , ex vivo , transforming growth factor , matrix metalloproteinase , andrology , chemistry , pathology , anatomy , biochemistry , alternative medicine , in vitro , gene
There is no curative treatment that modifies the structure of the damaged articular cartilage. This study examined the effect of melatonin (MT) with or without treadmill exercise (Ex) on aberrant chondrocyte behavior. MT was injected twice/day subcutaneously and Ex was conducted for 1 h/day. The interventions were initiated 4 weeks after an intra‐articular collagenase injection, and were maintained for 4 weeks. Vehicle treatment (Veh) elevated the joint parameters, while MT with or without Ex restored them to the control levels. Intervention reduced the levels of both serum TNF‐α and its downstream molecules Hif‐2a and Runx2. COL2A1 was over‐expressed and cleaved in the Veh and MT alone groups, while active MMP‐13 was the same in all groups. Intervention decreased the cleaved caspase‐3 level regardless of the type, whereas LC3 II expression was abolished in MT+Ex only. Combined intervention induced the upregulation of TGF‐ β1 gene expression, with lower ALP levels. Consistent with this, histological repair was stimulated in the MT+Ex group. These findings suggest that melatonin combined with exercise blocks the TNF‐α‐mediated death signal via TGF‐β1 upregulation, leading to cartilage recovery in the osteoarthritic rats. Key words : Osteoarthritic cartilage, Melatonin, Treadmill exercise, Cell death, TGF‐β1