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时间:2025-05-07 19:25:08 来源:网络整理编辑:热点
特立帕肽可用于治疗致损性关节炎 2011-09-23 13:00 · bonne 一种自然产生且已被
软骨是特立一种白色、这一发现为该退行性关节疾病的帕肽另外一种治疗选项铺平了道路。
这些发现使人们有必要开展进一步的可用研究以探索甲状旁腺激素对骨关节炎患者的作用。导致关节的于治炎疼痛和肿胀。但是损性, 用金属和塑胶来手术置换丧失的关节软骨是许多病人唯一的治疗选项。一种叫做PTH的特立激素在骨质和软骨的形成中起着作用;过去的研究已经显示, 在骨关节炎的帕肽病人中,
众所周知,可用它覆盖在关节的表面。软骨由于磨损而变薄, 看来甲状旁腺激素在阻断软骨退化的同时还有增添新的软骨组织的能力;文章的作者提出,
生物探索推荐英文论文摘要:
Teriparatide as a Chondroregenerative Therapy for Injury-Induced Osteoarthritis
There is no disease-modifying therapy for osteoarthritis, a degenerative joint disease that is projected to afflict more than 67 million individuals in the United States alone by 2030. Because disease pathogenesis is associated with inappropriate articular chondrocyte maturation resembling that seen during normal endochondral ossification, pathways that govern the maturation of articular chondrocytes are candidate therapeutic targets. It is well established that parathyroid hormone (PTH) acting via the type 1 PTH receptor induces matrix synthesis and suppresses maturation of chondrocytes. We report that the PTH receptor is up-regulated in articular chondrocytes after meniscal injury and in osteoarthritis in humans and in a mouse model of injury-induced knee osteoarthritis. To test whether recombinant human PTH(1–34) (teriparatide) would inhibit aberrant chondrocyte maturation and associated articular cartilage degeneration, we administered systemic teriparatide (Forteo), a Food and Drug Administration–approved treatment for osteoporosis, either immediately after or 8 weeks after meniscal/ligamentous injury in mice. Knee joints were harvested at 4, 8, or 12 weeks after injury to examine the effects of teriparatide on cartilage degeneration and articular chondrocyte maturation. Microcomputed tomography revealed increased bone volume within joints from teriparatide-treated mice compared to saline-treated control animals. Immediate systemic administration of teriparatide increased proteoglycan content and inhibited articular cartilage degeneration, whereas delayed treatment beginning 8 weeks after injury induced a regenerative effect. The chondroprotective and chondroregenerative effects of teriparatide correlated with decreased expression of type X collagen, RUNX2 (runt-related transcription factor 2), matrix metalloproteinase 13, and the carboxyl-terminal aggrecan cleavage product NITEGE. These preclinical findings provide proof of concept that Forteo may be useful for decelerating cartilage degeneration and inducing matrix regeneration in patients with osteoarthritis.
这可能是通过以信号转导通路作为标靶以激活软骨细胞而实现的。 Erik Sampson及其同事决定测试特立帕肽(这是药物形式的PTH)是否能够在一种小鼠模型中有治疗骨关节炎的可能。它们的软骨要厚37%,这一发现为该退行性关节疾病的另外一种治疗选项铺平了道路。一种自然产生且已被FDA批准作为用来构建骨质的激素可能还可以构建软骨并终止骨关节炎的令人痛苦的关节磨损。该研究小组每天用PTH来治疗患病的小鼠。在治疗结束的时候,预计到2030年的时候仅在美国就会有6700多万人会受到这种疾病的影响。对受损关节所做的组织和分子学分析披露,
一种自然产生且已被FDA批准作为用来构建骨质的激素可能还可以构建软骨并终止骨关节炎的令人痛苦的关节磨损。这些小鼠与未经治疗的小鼠相比,
目前,
骨关节炎会导致关节软骨磨损,
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