BACKGROUND: Destruction of cartilage in osteoarthritis is a direct effect of an imbalance between catabolic and anabolic activities in the tissue. While a great deal is known about catabolism, we sought to determine the biochemical basis of the anabolic activity. METHODS: Cartilage was isolated from normal and osteoarthritic patients and subjected to both cell and explant culture. mRNA expression levels of the growth and differentiation factors bone morphogenetic protein-2 (BMP-2), BMP-4, BMP-6, cartilage-derived morphogenetic protein-1 (CDMP-1), connective tissue growth factor (CTGF), and activin were determined. BMP-2 was localized in osteoarthritic cartilage by immunohistochemistry. To determine the mechanism of BMP-2 stimulation, chondrocytes were cultured with TGF-beta (transforming growth factor-beta), insulin-like growth factor-1 (IGF-1), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha). The BMP-2 response was monitored by quantitative real-time polymerase chain reaction to ascertain mRNA levels and by Western blot analysis, BMP-2 protein quantitation, and immunohistochemistry to determine protein levels. RESULTS: BMP-2 was found to be up-regulated in osteoarthritic chondrocytes and cartilage. In cell culture, IL-1beta and TNF-alpha increased BMP-2 mRNA and protein levels by eightfold and fifteenfold, respectively, whereas IGF-1 and TGF-beta1 had no effect. In cartilage explant cultures, IL-1beta and TNF-alpha increased BMP-2 levels both intracellularly and extracellularly. Functional relevance was suggested by co-localization of BMP-2 and newly synthesized type-II procollagen within the same cells. CONCLUSIONS: BMP-2 acts as a stimulus of anabolic activities in normal and osteoarthritic chondrocytes. Furthermore, the pro-inflammatory cytokines IL-1beta and TNF-alpha, known to be present in synovium and cartilage of patients with osteoarthritis, stimulate the production of active BMP-2.
BACKGROUND: Destruction of cartilage in osteoarthritis is a direct effect of an imbalance between catabolic and anabolic activities in the tissue. While a great deal is known about catabolism, we sought to determine the biochemical basis of the anabolic activity. METHODS:Cartilage was isolated from normal and osteoarthritic patients and subjected to both cell and explant culture. mRNA expression levels of the growth and differentiation factors bone morphogenetic protein-2 (BMP-2), BMP-4, BMP-6, cartilage-derived morphogenetic protein-1 (CDMP-1), connective tissue growth factor (CTGF), and activin were determined. BMP-2 was localized in osteoarthritic cartilage by immunohistochemistry. To determine the mechanism of BMP-2 stimulation, chondrocytes were cultured with TGF-beta (transforming growth factor-beta), insulin-like growth factor-1 (IGF-1), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha). The BMP-2 response was monitored by quantitative real-time polymerase chain reaction to ascertain mRNA levels and by Western blot analysis, BMP-2 protein quantitation, and immunohistochemistry to determine protein levels. RESULTS:BMP-2 was found to be up-regulated in osteoarthritic chondrocytes and cartilage. In cell culture, IL-1beta and TNF-alpha increased BMP-2 mRNA and protein levels by eightfold and fifteenfold, respectively, whereas IGF-1 and TGF-beta1 had no effect. In cartilage explant cultures, IL-1beta and TNF-alpha increased BMP-2 levels both intracellularly and extracellularly. Functional relevance was suggested by co-localization of BMP-2 and newly synthesized type-II procollagen within the same cells. CONCLUSIONS:BMP-2 acts as a stimulus of anabolic activities in normal and osteoarthritic chondrocytes. Furthermore, the pro-inflammatory cytokines IL-1beta and TNF-alpha, known to be present in synovium and cartilage of patients with osteoarthritis, stimulate the production of active BMP-2.
Authors: K V Greco; A J Iqbal; L Rattazzi; G Nalesso; N Moradi-Bidhendi; A R Moore; M B Goldring; F Dell'Accio; M Perretti Journal: Biochem Pharmacol Date: 2011-09-16 Impact factor: 5.858
Authors: Anna Csiszar; Mansoor Ahmad; Kira E Smith; Nazar Labinskyy; Qun Gao; Gabor Kaley; John G Edwards; Michael S Wolin; Zoltan Ungvari Journal: Am J Pathol Date: 2006-02 Impact factor: 4.307
Authors: Jason T Rich; Ivana Rosová; Jan A Nolta; Terence M Myckatyn; Linda J Sandell; Audrey McAlinden Journal: Biochem Biophys Res Commun Date: 2008-05-13 Impact factor: 3.575
Authors: N Chinzei; R H Brophy; X Duan; L Cai; R M Nunley; L J Sandell; M F Rai Journal: Osteoarthritis Cartilage Date: 2018-01-31 Impact factor: 6.576