New developments in the pathogenesis of articular cartilage calcification

Abstract

Articular cartilage, unlike growth plate cartilage, is specialized to not undergo matrix calcification. However, articular cartilage mineralization, in the form of CPPD (chondrocalcinosis) and hydroxyapatite crystals, frequently accompanies and complicates osteoarthritis and aging. Recent work has demonstrated that certain features of growth cartilage development and mineralization are shared in degenerative cartilage. These include chondrocyte proliferation, hypertrophy and increased apoptosis. Moreover, parathyroid hormone related protein (PTHrP), one of the central mediators of endochondral development, is abundant in osteoarthritic cartilage. Cartilage PPi elaboration and cytosolic transglutaminase activity are markedly increased with aging. Only recently have the molecular identities been defined for the chondrocyte inorganic pyrophosphate (PPi)-generating isozymes of the phosphodiesterase nucleotide pyrophosphatase (PDNP) family (including PC-1 and B10), and for transglutaminase in articular cartilage. This review focuses on the evolving understanding of the potential roles, in articular cartilage calcification, of PTHrP, PDNP family enzymes, PPi metabolism, and transglutaminase activity.

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

“…10) A decrease in the amount of ECM, hypertrophic differentiation of mature chondrocytes and ectopic mineralization have been observed in the articular cartilage of patients with OA. [13][14][15][38][39][40] Therefore, the ectopic mineralization in OA likely at least partly results from abrogation of the suppressive effect of ALP activity by decreasing the amount of ECM around the chondrocytes.…”

“…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.…”

Hydroxyapatite deposition disease of the joint

“…Degenerative cartilage has a greater ability to generate crystals [28]. The expression of transforming growth factor-beta, interleukin-1-beta and insulin-like growth factor-1, as well as the amount of available adenosine triphosphate in degenerated cartilage, may help determine whether CPPD or BCP crystals are deposited in the altered matrix [29]. However, more than one source of formation is likely.…”

Pathogenesis of cartilage calcification: Mechanisms of crystal deposition in cartilage

“…Cartilage mineralization also occurs as an unwanted aberrant phenomenon in hyaline cartilage (articular cartilage at long and flat bone joint surfaces) [4][5][6][7][8], within the intervertebral disk [9,10], in the meniscus [11], and within other tissues containing mixtures of hyaline cartilage and fibrocartilage, such as auricular [12], thyroid [13•], and tracheal cartilage [14]. Physiologic mineral provides mechanical strength to the tissue, whereas the dystrophic and aberrant calcifications contribute to the wear of the tissues in which they occur [15•,16,17].…”