Abstract
Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca2+-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.
Highlights
Osteoarthritis (OA), the most common disease of synovial joints, is characterized by whole joint failure including cartilage degeneration and subchondral bone changes
To provide a better understanding of the interaction between the extracellular matrix (ECM) and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1)
Varus knee alignment leads to an unequal loading of the tibial plateau and alterations were always compared between the medial and lateral compartments
Summary
Osteoarthritis (OA), the most common disease of synovial joints, is characterized by whole joint failure including cartilage degeneration and subchondral bone changes. Thrombospondins (TSPs) are a family of five oligomeric glycoproteins (TSP-1 to TSP-5) that bind to collagens but are involved in their secretion and assembly [4,5,6]. They bind Ca2+ and undergo calcium-dependent conformational changes that are important for their function. COMP accelerates collagen fibrillogenesis and regulates chondrocyte proliferation and matrix assembly [4,8] It is widely used as a serum marker for OA and its level correlates with disease severity, but its function in OA is still unknown [9,10]. TSP-1 is an antiangiogenic factor [11], and OA progression is suppressed through an increased TSP-1 expression via reduction of vascular density in articular cartilage [12]
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