Department of Orthopaedic Surgery, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
Department of Pathology, Otto-von-Guericke-University Magdeburg, Medical Faculty, Magdeburg, Germany.
Best Pract Res Clin Rheumatol. 2021 Dec;35(4):101722. doi: 10.1016/j.berh.2021.101722. Epub 2021 Oct 31.
Osteoarthritis (OA) is a degenerative joint disease characterized by progressive degeneration of articular cartilage. Due to its high prevalence and limited treatment options, OA has become one of the most disabling diseases in developed countries. In recent years, OA has been recognized as a heterogenic disease with various phenotypes. Calcium crystal-related endotypes, which are defined by either a distinct functional or pathobiological mechanism, are present in approximately 60% of all OA patients. Two different calcium crystals can accumulate in the joint and thereby calcify the cartilage matrix, which are basic calcium phosphate (BCP) and calcium pyrophosphate (CPP) crystals. The formation of these crystals depends mainly on the balance of phosphate and pyrophosphate, which is regulated by specific proteins controlling the pyrophosphate metabolism. Dysregulation of these molecules subsequently leads to preferential formation of either BCP or CPP crystals. BCP crystals, on the one hand, are directly associated with OA severity and cartilage degradation. They are mostly located in the deeper cartilage layers and are associated with chondrocyte hypertrophy. CPP crystal deposition, on the other hand, is a hallmark of chondrocalcinosis and is associated with aging and chondrocyte senescence. Therefore, BCP and CPP crystals are associated with different chondrocyte phenotypes. However, BCP and CPP crystals are not mutually exclusive and can coexist in OA, creating a mixed endotype of OA. Both crystals clearly play a role in the pathogenesis of OA. However, the exact impact of each crystal type on either driving the disease progression or being a result of chondrocyte differentiation is still to be elucidated.
骨关节炎（OA）是一种退行性关节疾病，其特征为关节软骨进行性退化。由于其高发病率和有限的治疗选择，OA 已成为发达国家最致残的疾病之一。近年来，OA 已被认为是一种具有多种表型的异质性疾病。钙晶体相关的内型，其由特定的功能或病理生物学机制定义，约存在于所有 OA 患者的 60%中。两种不同的钙晶体可以在关节中积聚并使软骨基质钙化，这两种晶体分别是羟基磷灰石（BCP）和焦磷酸钙（CPP）晶体。这些晶体的形成主要取决于磷酸盐和焦磷酸盐的平衡，而焦磷酸盐代谢则由控制焦磷酸盐代谢的特定蛋白质来调节。这些分子的失调随后导致 BCP 或 CPP 晶体的优先形成。一方面，BCP 晶体直接与 OA 的严重程度和软骨降解相关。它们主要位于较深的软骨层中，并与软骨细胞肥大有关。另一方面，CPP 晶体的沉积是软骨钙质沉着症的标志，与衰老和软骨细胞衰老有关。因此，BCP 和 CPP 晶体与不同的软骨细胞表型相关。然而，BCP 和 CPP 晶体并非相互排斥，它们可以共存于 OA 中，形成 OA 的混合内型。两种晶体都清楚地在 OA 的发病机制中发挥作用。然而，每种晶体类型对推动疾病进展或作为软骨细胞分化的结果的确切影响仍有待阐明。
