title: Chondroprotective effects of alpha-lipoic acid in a rat model of osteoarthritis.
abstract: OBJECTIVE
  The purpose of this study was to investigate whether alpha-lipoic acid (ALA) confers a chondroprotective effect on articular cartilage in rats with monosodium iodoacetate (MIA)-induced osteoarthritis (OA).
  
  
  METHODS
  Fifty male SD rats were divided into five groups, including SHAM-operated, MIA-induced OA, and three experimental groups treated with 50-, 100-, or 200-mg/kg ALA. After 14 d of ALA treatment, rats were sacrificed for joint macroscopic and histology assessments. The gene and protein expressions of markers related to chondrocyte phenotype, caspase proteins, NADPH oxidase 4 (Nox4), p22(phox), activation of nuclear factor-κB (NF-κB), and endoplasmic reticulum (ER) stress were measured by Western blot analyses or qRT-PCR.
  
  
  RESULTS
  The results showed that MIA injection successfully induced OA by causing cartilage degeneration. Morphological and histological examinations demonstrated that ALA treatment, especially 200 mg/kg of ALA, significantly ameliorated cartilage degeneration in rats with MIA-induced OA. ALA could effectively increase the levels of the collagen type II and aggrecan genes and inhibit apoptosis-related proteins expression. ALA reduced biomakers of oxidative damage and over-expression levels of Nox4 and p22(phox). ALA also suppressed ER stress and inhibited the activation of NF-κB pathway. Moreover, ALA obviously inhibited TNF-α secretion and Wnt/β-catenin signaling way.
  
  
  CONCLUSIONS
  These findings indicated that ALA might be a potential therapeutic agent for the protection of articular cartilage against progression of OA through inhibition of oxidative stress, ER stress, inflammatory cytokine secretion, and Wnt/β-catenin activation.
authors.affiliation: a Department of Orthopaedics , First Affiliated Hospital, Dalian Medical University , Dalian , China ;
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: b Department of Clinical Pharmacology, College of Pharmacy , Dalian Medical University , Dalian , China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.affiliation: a Department of Orthopaedics , First Affiliated Hospital, Dalian Medical University , Dalian , China ;
authors.forename: Zhuodong
authors.initials: Z
authors.lastname: Fu
authors.affiliation: a Department of Orthopaedics , First Affiliated Hospital, Dalian Medical University , Dalian , China ;
authors.forename: Mozhen
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D008063:Thioctic Acid
keywords: Alpha-lipoic acid (ALA); ER stress; NF-κB; osteoarthritis; oxidative stress