title: Anti-arthritic actions of β-cryptoxanthin against the degradation of articular cartilage in vivo and in vitro.
abstract: An inverse correlation between the morbidity of rheumatoid arthritis and daily intake of β-cryptoxanthin has been epidemiologically shown. In this study, we investigated the effects of β-cryptoxanthin on the metabolism of cartilage extracellular matrix in vivo and in vitro. Oral administration of β-cryptoxanthin (0.1-1 mg/kg) to antigen-induced arthritic rats suppressed the loss of glycosaminoglycans in articular cartilage, which is accompanied by the interference of aggrecanase-mediated degradation of aggrecan. Inhibition of the interleukin 1α (IL-1α)-induced aggrecan degradation by β-cryptoxanthin was also observed with porcine articular cartilage explants in culture. β-Cryptoxanthin (1-10 μM) dose-dependently down-regulated the IL-1α-induced gene expression of aggrecanase 1 (ADAMTS-4) and aggrecanase 2 (ADAMTS-5) in cultured human chondrocytes. Moreover, β-cryptoxanthin was found to augment the gene expression of aggrecan core protein in chondrocytes. These results provide novel evidence that β-cryptoxanthin exerts anti-arthritic actions and suggest that β-cryptoxanthin may be useful in blocking the progression of rheumatoid arthritis and osteoarthritis.
authors.affiliation: Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Imada
authors.affiliation: Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: Ayana
authors.initials: A
authors.lastname: Tsuchida
authors.affiliation: Institute of Fruit Tree and Tea Science, National Agriculture and Food Research Organization (NARO), Shizuoka, Shizuoka, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Matrix Biology, The Kennedy Institute of Rheumatology Division, Imperial College London, Hammersmith, London, United Kingdom.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Sofat
authors.affiliation: Department of Matrix Biology, The Kennedy Institute of Rheumatology Division, Imperial College London, Hammersmith, London, United Kingdom.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagase
authors.affiliation: The Institute for Social Medicine at Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan. Electronic address: satotak@toyaku.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
mesh_terms: D000071121:ADAMTS4 Protein / Q000235:genetics / Q000378:metabolism; D000071116:ADAMTS5 Protein / Q000235:genetics / Q000378:metabolism; D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy; D000072743:Beta-Cryptoxanthin / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009924:Organ Culture Techniques; D011917:Rats, Inbred Lew; D013552:Swine; D013582:Synovial Fluid / Q000166:cytology
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D018501:Antirheumatic Agents; D000072743:Beta-Cryptoxanthin; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D000071121:ADAMTS4 Protein
keywords: Aggrecanase; Carotenoid; Chondrocytes; Extracellular matrix; Osteoarthritis; Rheumatoid arthritis