Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020
Pentraxin 3 inhibits fibroblast growth factor 2 induced osteoclastogenesis in rheumatoid arthritis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhao Shuai, Wang Yiteng, Hou Linxin, Wang Yuejiao, Xu Neili, Zhang Ning
Аннотация
BACKGROUND: Synovial fibroblasts (SFs) act as key effector cells mediating synovial inflammation and joint destruction in rheumatoid arthritis (RA). Fibroblast growth factor 2 (FGF2) and its receptors (FGFRs) play important roles in RASF-mediated osteoclastogenesis. Pentraxin 3 (PTX3) is a soluble pattern recognition receptor with nonredundant roles in inflammation and innate immunity. PTX3 is produced by various cell types, including SFs and is highly expressed in RA. However, the role of PTX3 in FGF2-induced osteoclastogenesis in RA and the underlying mechanism have been poorly elucidated.
METHODS: We first determined the expression of FGF2 and RANKL in synovial tissue and synovial fluid of RA patients. We then examined the effect of PTX3 on RASF osteoclastogenesis induced by endogenous and exogenous FGF2 in isolated RASF cells treated with FGF2 and/or recombinant PTX3 (rPTX3). Thirdly, we analyzed the effect of PTX3 on FGF2 binding to FGFR-1 and HSPG receptors on RASFs. Lastly, we evaluated joint morphology after injection of rPTX3 into collagen-induced arthritis (CIA) mice.
RESULTS: FGF2 was confirmed to be highly expressed in both synovial tissue and synovial fluid of RA patients. FGF2 promoted cell proliferation and increased the expressions of RANKL and ICAM-1 and RANKL/OPG to induce osteoclastogenesis in RASF, while anti-FGF2 neutralized this effect. PTX3 significantly inhibited FGF2-induced RASF cell growth and osteoclastogenesis by preventing the interaction of 125I-FGF2 and FGFRs on the same cells. In addition, administration of rPTX3 significantly ameliorated cartilage and bone destruction in mice with CIA.
CONCLUSIONS: PTX3 exhibited an inhibitory effect on the autocrine and paracrine stimulation of FGF2 on SFs, and ameliorated bone destruction in CIA mice. PTX3 may be implicated in bone destruction in RA, which may provide theoretical evidence and potential therapeutic targets for RA treatment.
METHODS: We first determined the expression of FGF2 and RANKL in synovial tissue and synovial fluid of RA patients. We then examined the effect of PTX3 on RASF osteoclastogenesis induced by endogenous and exogenous FGF2 in isolated RASF cells treated with FGF2 and/or recombinant PTX3 (rPTX3). Thirdly, we analyzed the effect of PTX3 on FGF2 binding to FGFR-1 and HSPG receptors on RASFs. Lastly, we evaluated joint morphology after injection of rPTX3 into collagen-induced arthritis (CIA) mice.
RESULTS: FGF2 was confirmed to be highly expressed in both synovial tissue and synovial fluid of RA patients. FGF2 promoted cell proliferation and increased the expressions of RANKL and ICAM-1 and RANKL/OPG to induce osteoclastogenesis in RASF, while anti-FGF2 neutralized this effect. PTX3 significantly inhibited FGF2-induced RASF cell growth and osteoclastogenesis by preventing the interaction of 125I-FGF2 and FGFRs on the same cells. In addition, administration of rPTX3 significantly ameliorated cartilage and bone destruction in mice with CIA.
CONCLUSIONS: PTX3 exhibited an inhibitory effect on the autocrine and paracrine stimulation of FGF2 on SFs, and ameliorated bone destruction in CIA mice. PTX3 may be implicated in bone destruction in RA, which may provide theoretical evidence and potential therapeutic targets for RA treatment.