Calcification of articular cartilage in human osteoarthritis

Abstract

Objective. Hypertrophic chondrocyte differentiation is a key step in endochondral ossification that produces basic calcium phosphates (BCPs). Although chondrocyte hypertrophy has been associated with osteoarthritis (OA), chondrocalcinosis has been considered an irregular event and linked mainly to calcium pyrophosphate dihydrate (CPPD) deposition. The aim of this study was to determine the prevalence and composition of calcium crystals in human OA and analyze their relationship to disease severity and markers of chondrocyte hypertrophy.Methods. One hundred twenty patients with endstage OA undergoing total knee replacement were prospectively evaluated. Cartilage calcification was studied by conventional x-ray radiography, digital-contact radiography (DCR), field-emission scanning electron microscopy (FE-SEM), and synovial fluid analysis. Cartilage calcification findings were correlated with scores of knee function as well as histologic changes and chondrocyte hypertrophy as analyzed in vitro.Results. DCR revealed mineralization in all cartilage specimens. Its extent correlated significantly with the Hospital for Special Surgery knee score but not with age. FE-SEM analysis showed that BCPs, rather than CPPD, were the prominent minerals. On histologic analysis, it was observed that mineralization correlated with the expression of type X collagen, a marker of chondrocyte hypertrophy. Moreover, there was a strong correlation between the extent of mineralization in vivo and the ability of chondrocytes to produce BCPs in vitro. The induction of hypertrophy in healthy human chondrocytes resulted in a prominent mineralization of the extracellular matrix.Conclusion. These results indicate that mineralization of articular cartilage by BCP is an indissociable process of OA and does not characterize a specific subset of the disease, which has important consequences in the development of therapeutic strategies for patients with OA.Osteoarthritis (OA) is the most common joint disorder and is characterized by cartilage loss, new bone formation at the margins of the joints (osteophytes), changes in subchondral bone, and recurrent synovitis. The incidence of OA increases with age. Calcium pyrophosphate dihydrate (CPPD) crystals are known to cause acute attacks of pseudogout in the joints, but crystal deposition has also been reported to be associated with OA (1). Aside from CPPD crystals, basic calcium phosphates (BCPs), such as carbonatesubstituted hydroxyapatite (HA), tricalcium phosphate, and octacalcium phosphate, have been found in the synovial fluid (SF), synovium, and cartilage from patients with OA (2-4). The data concerning the distribution and frequency of their occurrence vary, depending on patient selection and crystal identification methods (5-7). Identification of BCP crystals in OA

Supplemented Chondroitin Sulfate and Hyaluronic Acid Suppress Mineralization of the Chondrogenic Cell Line, ATDC5, <i>via</i> Direct Inhibition of Alkaline Phosphatase

“…11,12) Although the mineralization of chondrocytes is essential for osteogenesis, ectopic mineralization in articular cartilage induced by hypertrophic chondrocytes in patients with osteoarthritis (OA) causes cartilage degeneration. [13][14][15][16] Alkaline phosphatase (ALP) is located on the cell surface of chondrocytes and hydrolyzes pyrophosphoric acid to inorganic phosphoric acid, thereby supplying the substrate necessary for mineralization. [17][18][19][20] The inorganic phosphoric acid taken into chondrocytes via a phosphate transporter binds to calcium present in the cells to form calcium phosphate crystals; this process is termed mineralization.…”

Basic Calcium Phosphate Crystals Induce Monocyte/Macrophage IL-1β Secretion through the NLRP3 Inflammasome In Vitro

“…Articular cartilage calcification is associated with severe osteoarthritis (OA) and destructive arthropathies, such as Milwaukee shoulder syndrome. Interestingly, BCP crystals are detected in 100% of knee and hip osteoarthritic cartilages harvested at the time of total joint arthroplasty (1,2). BCP crystal deposition in knee articular cartilage is correlated with cartilage destruction and more severe lesions (1).…”

“…Interestingly, BCP crystals are detected in 100% of knee and hip osteoarthritic cartilages harvested at the time of total joint arthroplasty (1,2). BCP crystal deposition in knee articular cartilage is correlated with cartilage destruction and more severe lesions (1). Their presence in synovial fluid predicts radiological OA progression (3).…”

Osteoarthritis – the role of cartilage and capability of modification of the course of disease

“…Wzrost uwapnienia chrząstki koreluje z zaawansowaniem choroby zwyrodnieniowej. Udowodniono też, że może być on czynnikiem pobudzającym produkcję mediatorów zapalenia przez komórki chrzęstne [11].…”