Matrix proteins promote matrix vesicle mineralization

描述（由申请人提供）：致病性钙晶体，包括焦磷酸钙（CPPD）和碱性磷酸钙（BCP）晶体是骨关节炎关节的常见成分。这些晶体可以识别出异常严重、进展迅速的关节炎患者。然而，晶体如何在通常未矿化的关节软骨基质中形成仍不清楚。基质囊泡是膜结合的，软骨细胞衍生的，与钙晶体形成有关的细胞外细胞器。初步结果表明，软骨周围的细胞外基质明显影响基质囊泡矿化的能力。在生长板软骨中，基质囊泡与其周围的细胞外环境之间存在着重要的相互作用。骨关节炎和钙晶体沉积时，关节软骨基质会发生剧烈变化，但对关节软骨细胞外基质和基质囊泡的相互作用知之甚少。我们假设基质囊泡和细胞外基质组分之间的相互作用强烈影响关节软骨基质囊泡产生病理性钙晶体的能力。

DESCRIPTION (provided by applicant): 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.