颗粒蛋白前体与骨关节疾病的相关性

Relationship between progranulin and osteoarthropathy

颗粒蛋白前体(progranulin,PGRN)作为体内的自分泌性生长因子,近些年研究发现其除了与神经系统等密切相关外,还与临床骨关节疾病密切相关。在类风湿关节炎,PGRN可通过与肿瘤坏死因子α(tumor necrosis factorsα,TNF-α)竞争性结合肿瘤坏死因子受体(tumor necrosis factor receptor,TNFR)抑制类风湿关节炎的进展;在骨性关节炎(osteoarthritis,OA),PGRN可抑制白细胞介素1b(interleukin-1b,IL-1b)介导的软骨细胞分解,并通过TNFR2/14-3-3ε信号通路促进软骨形成;在腰椎间盘突出症,目前报道较少,尚待进一步研究认识其相互关系;在绝经后骨质疏松症,结合相关文献报道,推测绝经后骨质疏松症可能是由于绝经后雌激素缺乏,体内PGRN表达下降,雌激素受体α(estrogen receptorα,ERα)泛素化增加而表达减少,进而通过影响前成骨细胞和破骨细胞导致骨质疏松。本文对相关文献进行综述,为PGRN在骨关节疾病的临床研究和应用提供参考。

As an autocrine growth factor in vivo,progranulin(PGRN)has been found to be closely related not only to the nervous system,but also to bone and joint diseases.In rheumatoid arthritis,PGRN inhibits the progression of arthritis by competing with tumor necrosis factorsα(TNF-α)to bind with tumor necrosis factor receptor(TNFR).In osteoarthritis,PGRN inhibits interleukin-1b(IL-1b)-mediated chondrocytic decomposition and promotes cartilage formation via TNFR2/14-3-3εsignaling pathway.The relationship between PGRN and lumbar disc herniation is poorly reported and needs further study.In osteoporosis,combined with the related literature reports,we postulate postmenopausal osteoporosis may be due to estrogen deficiency,decreased PGRN expression,increased ERαubiquitination and decreased ERαexpression in postmenopausal women.This article reviews the related literatures and provides references for the clinical research and application of PGRN in osteoarthropathy.