Point: Hydroxyapatite crystal deposition is intimately involved in the pathogenesis and progression of human osteoarthritis

Abstract

The cause of osteoarthritis (OA), the most common form of arthritis, is most likely multifactorial. No drug exists to slow the progression or reverse OA disease progression. Ample data support a key role of calcium-containing crystals, such as hydroxyapatite, in OA pathogenesis. The presence of these crystals, far higher in OA than in any other form of arthritis, correlates with the degree of radiographic degeneration. Calcium-containing crystals have potent biologic effects in vitro that emphasize their pathogenic potential. OA-associated matrix and chondrocyte alterations play an intimate role in the crystal deposition process. A major difficulty has been the lack of a simple technique for crystal identification in affected joints. Enhanced effort is needed to establish calcium-containing crystals as a therapeutic target in OA, as current data suggest an intimate association in its pathogenesis and progression.

NLRP3 inflammasome plays a critical role in the pathogenesis of hydroxyapatite-associated arthropathy

“…NLRP3 and ASC, components of the NLRP3 inflammasome, which can activate IL-1β secretion in response to a number of crystalline agonists, were required for this inflammatory response. As hydroxyapatite crystals have been described to be predominant in OA joints (15), we speculated that HA crystals might be the factor within OA synovial fluid that stimulates IL-1β production via activation of the NLRP3 inflammasome. To characterize the inflammatory property of HA crystals, peritoneal macrophages derived from wild-type (WT) mice were primed with LPS and stimulated with different forms of synthetic HA crystals for 8 h (Fig.…”

“…Intraarticular deposition of HA crystals occurs in up to 70% of OA cases and strongly correlates with the severity of cartilage deterioration (14)(15)(16). Abnormal accumulation of HA can provoke an acute arthritis in some occasions (17) and is also associated with other destructive arthropathies such as calcific periarthritis and Milwaukee shoulder syndrome (18).…”

Atherosclerosis: Viewing the Problem from a Different Perspective Including Possible Treatment Options

“…This event is preceded by a loss of mechanical structure in the arterial wall. Once Ca-HAP is deposited, it is unlikely to be reabsorbed because the solubility product constant K sp is very small, and the large stores of Ca +2 and PO 4 −3 in the bones oppose any attempts to dissolve Ca-HAP due to the common ion effect. Investigating the differences in affinity for hydrolysis products of cholesterol ester intermediates between Ca-HAP and lipoproteins such as HDL, LDL, and VLDL, using isothermic titration calorimetry, could lead to the development of a new class of medications targeted at the deposition of cholesterol within Ca-HAP.…”

“…Osteoarthritis is characterized by depositions of Ca-HAP that is commonly associated with structural deterioration of the joint from trauma and loss of cartilage. 4 4. Pancreatic, granulomatous and neoplastic diseases develop partitions of calcium within the tissue to possibly separate disease and non-disease zones (Fig.…”

Osteoarthritis, a basic calcium phosphate crystal–associated arthropathy? Comment on the article by Fuerst et al

“…Additionally, Cheung et al showed that treatment with phosphocitrate, an antimineralizing agent, reduced meniscus calcifications and OA lesions in guinea pigs (5). Finally, in vitro, BCPs display mitogenic, catabolic, apoptotic, and inflammatory properties (6,7).…”