EDIL3 在维持软骨细胞外基质和抑制骨关节炎发展中的作用

IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING
Mei-Feng Chen, Chih-Chien Hu, Yung-Heng Hsu, Yu-Chih Lin, Kai-Lin Chen, Steve W. N. Ueng, Yuhan Chang
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引用次数: 0

摘要

目的:需要预防软骨细胞丢失、细胞外基质(ECM)降解和骨关节炎(OA)进展的治疗药物。损伤软骨中表皮生长因子(EGF)样重复序列和盘状蛋白i样结构域蛋白3 (EDIL3)的表达水平显著高于未损伤软骨。然而,EDIL3对软骨的影响尚不清楚。方法采用人软骨塞(离体)和自发性OA小鼠(体内),探讨EDIL3是否通过改变OA相关指标具有软骨保护作用。结果EDIL3蛋白抑制软骨细胞聚集,维持软骨细胞数量和SOX9表达。EDIL3蛋白通过维持透明软骨中的软骨细胞数量和基质生成软骨细胞(MPCs)的数量来阻止STR/ort小鼠OA的进展。它降低了聚集蛋白的降解、基质金属蛋白酶(MMP)-13的表达、国际骨关节炎研究学会(OARSI)评分和骨重塑。它增加了软骨下骨板的孔隙度。EDIL3抗体增加了软骨中不产生基质的软骨细胞(mnc)的数量,并增加了oa相关的促炎细胞因子的血清浓度,包括单核细胞趋化蛋白-3 (MCP-3)、RANTES、白细胞介素(IL)-17A、IL-22和GROα。给予β1和β3整合素激动剂(CD98蛋白)可增加OA小鼠SOX9的表达。因此,EDIL3可能激活β1和β3整合素来保护软骨。EDIL3还可能通过减弱软骨细胞中il -1β增强的磷酸激酶蛋白的表达,特别是糖原合成酶激酶3α/β (GSK-3α/β)和磷脂酶C γ1 (PLC-γ1)的表达来保护软骨。结论EDIL3具有维持软骨ECM、抑制骨性关节炎发展的作用,是治疗骨性关节炎的潜在药物。本文引自:骨关节,2023;12(12):734-746。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The role of EDIL3 in maintaining cartilage extracellular matrix and inhibiting osteoarthritis development
Aims Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown. Methods We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators. Results EDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and bone remodelling. It increased the porosity of the subchondral bone plate. Administration of an EDIL3 antibody increased the number of matrix-non-producing chondrocytes (MNCs) in cartilage and exacerbated the serum concentrations of OA-related pro-inflammatory cytokines, including monocyte chemotactic protein-3 (MCP-3), RANTES, interleukin (IL)-17A, IL-22, and GROα. Administration of β1 and β3 integrin agonists (CD98 protein) increased the expression of SOX9 in OA mice. Hence, EDIL3 might activate β1 and β3 integrins for chondroprotection. EDIL3 may also protect cartilage by attenuating the expression of IL-1β-enhanced phosphokinase proteins in chondrocytes, especially glycogen synthase kinase 3 alpha/beta (GSK-3α/β) and phospholipase C gamma 1 (PLC-γ1). Conclusion EDIL3 has a role in maintaining the cartilage ECM and inhibiting the development of OA, making it a potential therapeutic drug for OA. Cite this article: Bone Joint Res 2023;12(12):734–746.
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来源期刊
Bone & Joint Research
Bone & Joint Research CELL & TISSUE ENGINEERING-ORTHOPEDICS
CiteScore
7.40
自引率
23.90%
发文量
156
审稿时长
12 weeks
期刊介绍: The gold open access journal for the musculoskeletal sciences. Included in PubMed and available in PubMed Central.
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