title: Betulin suppressed interleukin-1β-induced gene expression, secretion and proteolytic activity of matrix metalloproteinase in cultured articular chondrocytes and production of matrix metalloproteinase in the knee joint of rat.
abstract: We investigated whether betulin affects the gene expression, secretion and proteolytic activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well asin vivoproduction of MMP-3 in the rat knee joint to evaluate the potential chondroprotective effect of betulin. Rabbit articular chondrocytes were cultured and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure interleukin-1β (IL-1β)-induced gene expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen. Effect of betulin on IL-1β-induced secretion and proteolytic activity of MMP-3 was investigated using western blot analysis and casein zymography, respectively. Effect of betulin on MMP-3 protein production was also examinedin vivo. The results were as follows: (1) betulin inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5, but increased the gene expression of type II collagen; (2) betulin inhibited the secretion and proteolytic activity of MMP-3; (3) betulin suppressed the production of MMP-3 proteinin vivo. These results suggest that betulin can regulate the gene expression, secretion, and proteolytic activity of MMP-3, by directly acting on articular chondrocytes.
authors.affiliation: Department of Orthopedic Surgery, Gangneung Asan Hospital, College of Medicine, University of Ulsan, Gangneung 25440, Korea.
authors.forename: Ho Jong
authors.initials: HJ
authors.lastname: Ra
authors.affiliation: Department of Health Management, Sahmyook University, Seoul 01795, Korea.
authors.forename: Hyun Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Ho Seung
authors.initials: HS
authors.lastname: Jo
authors.affiliation: Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Dae Cheol
authors.initials: DC
authors.lastname: Nam
authors.affiliation: Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Young Bok
authors.initials: YB
authors.lastname: Lee
authors.affiliation: Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Byeong Hun
authors.initials: BH
authors.lastname: Kang
authors.affiliation: Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Dong Kyu
authors.initials: DK
authors.lastname: Moon
authors.affiliation: Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Choong Jae
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Sun-Chul
authors.initials: SC
authors.lastname: Hwang
keywords: Betulin; Chondrocyte; Metalloproteinase; Osteoarthritis