Pathogenic calcium crystals, including calcium pyrophosphate (CPPD) and basic calcium phosphate (BCP) crystals are common components of osteoarthritic joints. These crystals identify a subset of patients with unusually severe, rapidly progressive, arthritis. Yet, how crystals form in the normally unmineralized articular cartilage matrix remains unknown. Matrix vesicles are membrane-bound, chondrocyte-derived, extracellular organelles implicated in calcium crystal formation. Preliminary findings strongly suggest that the surrounding extracelllular matrix in cartilage clearly influences the matrix vesicle's ability to mineralize. There is ample precedence for an important interaction between matrix vesicles and their surrounding extracellular environment in growth plate cartilage. While dramatic changes in articular cartilage matrix occur in both osteoarthritis and with calcium crystal deposition, little is known about the interaction of extracellular matrix and matrix vesicles in articular cartilage. We hypothesize that interactions between matrix vesicles and extracellular matrix components strongly influence the ability of articular cartilage matrix vesicles to generate pathologic calcium crystals. In this proposal, we will will use porcine articular cartilage matrix vesicles in a gel-based calcification model to study I) the effects of type II collagen on articular cartilage matrix vesicle mineralization, II) the effects of large and small proteoglycans on articular cartilage matrix vesicle mineralization, and IN) the effects of the calcium binding proteins (osteopontin, SPARC, and matrix gla protein) on articular cartilage matrix vesicle mineralization. The ultimate goal of this work is to understand the pathogenesis of calcium crystal formation in articular cartilage, so that specific therapies for this disabling disease can be designed.
| Uzuki, Miwa; Sawai, Takashi; Ryan, Lawrence M et al. (2014) Upregulation of ANK protein expression in joint tissue in calcium pyrophosphate dihydrate crystal deposition disease. J Rheumatol 41:65-74 |
| Rosenthal, Ann K (2011) Crystals, inflammation, and osteoarthritis. Curr Opin Rheumatol 23:170-3 |
| Rosenthal, Ann K; Gohr, Claudia M; Ninomiya, James et al. (2010) Proteomic analysis of articular cartilage vesicles from normal and osteoarthritic cartilage. Arthritis Rheum : |
| Rosenthal, Ann K (2009) Calcium crystals and arthritis: what is new under polarizing light? J Clin Rheumatol 15:42-5 |
| Jubeck, Brian; Muth, Emily; Gohr, Claudia M et al. (2009) Type II collagen levels correlate with mineralization by articular cartilage vesicles. Arthritis Rheum 60:2741-6 |
| Mitton, Elizabeth; Gohr, Claudia M; McNally, Mark T et al. (2009) Articular cartilage vesicles contain RNA. Biochem Biophys Res Commun 388:533-8 |
| Rosenthal, A K; Mattson, E; Gohr, C M et al. (2008) Characterization of articular calcium-containing crystals by synchrotron FTIR. Osteoarthritis Cartilage 16:1395-402 |
| Jubeck, Brian; Gohr, Claudia; Fahey, Mark et al. (2008) Promotion of articular cartilage matrix vesicle mineralization by type I collagen. Arthritis Rheum 58:2809-17 |
| Orlov, Nikita; Shamir, Lior; Macura, Tomasz et al. (2008) WND-CHARM: Multi-purpose image classification using compound image transforms. Pattern Recognit Lett 29:1684-1693 |
| Rosenthal, Ann K; Fahey, Mark; Gohr, Claudia et al. (2008) Feasibility of a tetracycline-binding method for detecting synovial fluid basic calcium phosphate crystals. Arthritis Rheum 58:3270-4 |
Showing the most recent 10 out of 13 publications
