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首页> 外文期刊>The journal of clinical investigation >Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis
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Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

机译：催乳素可促进软骨存活并减轻炎症性关节炎中的炎症

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Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3–dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor–null ( Prlr~(–/–) ) mice. Moreover, eliciting hyperprolactinemia in rats before or after inducing the adjuvant model of inflammatory arthritis reduced chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, bone erosion, joint swelling, and pain. These results reveal the protective effect of PRL against inflammation-induced chondrocyte apoptosis and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage and inflammation in RA.
机译：软骨细胞是软骨中唯一的细胞，它们在凋亡中的死亡会导致炎症性关节疾病（如类风湿关节炎（RA））中的软骨丢失。公认的RA治疗干预措施是抑制凋亡介导的软骨降解。激素催乳素（PRL）在RA患者的循环中经常增加，但是高催乳素血症在疾病活动中的作用尚不清楚。在这里，我们证明PRL通过阻止p53的诱导并通过降低BAX / BCL-2的比例来抑制促炎细胞因子（TNF-α，IL-1β和IFN-γ）混合物对培养的软骨细胞凋亡的作用。一种非NO依赖性，JAK2 / STAT3依赖性途径。 PRL局部治疗或增加PRL循环水平还可以通过向大鼠的膝关节注射细胞因子来预防软骨细胞凋亡，而在PRL受体-空（Prlr〜（-/-））小鼠中，细胞因子的促凋亡作用增强。此外，在诱导炎性关节炎的佐剂模型之前或之后引发大鼠高泌乳素血症可减少软骨细胞凋亡，促炎细胞因子表达，pan的形成，骨侵蚀，关节肿胀和疼痛。这些结果揭示了PRL对炎症诱导的软骨细胞凋亡的保护作用和高泌乳素血症的治疗潜力，以减少RA中的永久性关节损伤和炎症。

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