Effect of lncRNA HAGLR on pyroptosis of chondrocytes in osteoarthritis and its mechanism

MENG Xiao-yuan; MA Le; NING Kai; AN Meng-yu

doi:10.11659/jjssx.10E025002

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Effect of lncRNA HAGLR on pyroptosis of chondrocytes in osteoarthritis and its mechanism

Basic Research | 更新时间：2026-06-16

- Effect of lncRNA HAGLR on pyroptosis of chondrocytes in osteoarthritis and its mechanism
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 35, Issue 6, Pages: 491-496(2026)
- 作者机构：
  
  1.新疆维吾尔自治区人民医院骨科中心关节运动病区，新疆乌鲁木齐830001
  2.新疆维吾尔自治区人民医院麻醉手术中心，新疆乌鲁木齐 830001
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.10E025002
  CLC： R684.3
- Received：03 October 2025，
  
  Published：25 June 2026
- 稿件说明：
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孟晓源,马乐,宁凯等.lncRNA HAGLR对骨关节炎软骨细胞焦亡的影响及机制研究[J].局解手术学杂志,2026,35(06):491-496.

MENG Xiao-yuan,MA Le,NING Kai,et al.Effect of lncRNA HAGLR on pyroptosis of chondrocytes in osteoarthritis and its mechanism[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(06):491-496.
孟晓源,马乐,宁凯等.lncRNA HAGLR对骨关节炎软骨细胞焦亡的影响及机制研究[J].局解手术学杂志,2026,35(06):491-496. DOI： 10.11659/jjssx.10E025002.

MENG Xiao-yuan,MA Le,NING Kai,et al.Effect of lncRNA HAGLR on pyroptosis of chondrocytes in osteoarthritis and its mechanism[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(06):491-496. DOI： 10.11659/jjssx.10E025002.

摘要

目的

探讨lncRNA HAGLR对骨关节炎（OA）软骨细胞焦亡的影响及机制。

方法

动物实验：将34只SD大鼠随机分为Saline组（左侧膝关节腔注射50 μL生理盐水）和OA模型组（左侧膝关节腔注射50 μL含5 mg碘乙酸单钠的生理盐水），每组17只。造模2周后，采用HE染色、番红O/固绿染色评估软骨组织损伤程度，qRT-PCR检测lncRNA HAGLR、miR-106b-5p表达，Western blot检测硫氧还蛋白互作蛋白（TXNIP）、NOD样受体热蛋白结构域相关蛋白3（NLRP3）、Caspase-1、消皮素D-N端（GSDMD-N）蛋白表达，ELISA测定血清白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）水平。体外实验：将人软骨细胞系C28/I2分为对照组（常规培养）、OA组（添加IL-1β 20 ng/mL刺激48 h构建体外OA模型）、si-NC组（转染si-NC 24 h后建模）、si-HAGLR组（转染si-HAGLR后建模）、mimic-NC组（转染mimic-NC后建模）、miR-106b-5p-mimic组（转染miR-106b-5p-mimic后建模）、si-HAGLR+miR-106b-5p-mimic组（共转染si-HAGLR和miR-106b-5p-mimic后建模）。采用CCK-8法检测细胞增殖活力，qRT-PCR检测lncRNA HAGLR、miR-106b-5p表达，免疫荧光染色和ELISA检测IL-1β、IL-18表达，Western blot检测TXNIP、NLRP3、Caspase-1、GSDMD-N蛋白表达，双荧光素酶报告基因实验验证lncRNA HAGLR与miR-106b-5p的靶向结合关系。

结果

动物实验：OA模型组大鼠软骨损伤较Saline组严重；与Saline组相比，OA模型组大鼠Mankin评分升高，lncRNA HAGLR、TXNIP、NLRP3、Caspase-1、GSDMD-N、IL-1β、IL-18表达上调，miR-106b-5p表达下调，差异均有统计学意义（

0.05）。体外实验：与对照组相比，OA组细胞中lncRNA HAGLR、TXNIP、NLRP3、Caspase-1、GSDMD-N、IL-1β、IL-18表达上调，细胞增殖活力降低，miR-106b-5p表达下调，差异均有统计学意义（

0.05）；与si-NC组相比，si-HAGLR组细胞中上述焦亡及炎症相关指标表达下调，细胞增

殖活力增加，miR-106b-5p表达上调，差异均有统计学意义（

0.05）；与mimic-NC组相比，miR-106b-5p-mimic组细胞中lncRNA HAGLR表达无显著变化（

0.05），miR-106b-5p表达上调（

0.05），细胞增殖活力增加（

0.05），TXNIP、焦亡相关蛋白和炎症相关指标下调（

0.05）；si-HAGLR+miR-106b-5p-mimic组细胞中上述焦亡及炎症相关指标表达进一步下调（

0.05），细胞增殖活力进一步增加（

0.05）。双荧光素酶报告基因实验证实lncRNA HAGLR与miR-106b-5p存在直接结合位点。

结论

lncRNA HAGLR通过靶向调控miR-106b-5p，促进TXNIP表达，并激活NLRP3/Caspase-1/GSDMD-N通路，从而诱导OA软骨细胞焦亡，加剧软骨细胞炎症和损伤。

Abstract

Objective

To investigate the effect of lncRNA HAGLR on pyroptosis of chondrocytes in osteoarthritis （OA） and its mechanism.

Methods

Animal experiment： Thirty-four SD rats were randomly divided into the Saline group （injected with 50 μL of normal saline into the left knee joint cavity） and the OA model group （injected with 50 μL of normal saline containing 5 mg monosodium iodoacetate into the left knee joint cavity），with 17 rats in each group.Two weeks after modeling，the degree of cartilage tissue injury was evaluated by HE staining and Safranin O/Fast green staining. The expressions of lncRNA HAGLR and miR-106b-5p were detected by qRT-PCR. The protein expressions of thioredoxin interacting protein （TXNIP），NOD-like receptor family pyrin domain containing 3 （NLRP3），Caspase-1，and gasdermin D N-terminal （GSDMD-N） were detected by Western blot. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by ELISA. In vitro experiments： The human chondrocyte cell line C28/I2 was divided into the following groups： the control group （cultured under normal conditions），OA group （stimulated with 20 ng/mL IL-1β for 48 hours to establish an in vitro OA model），si-NC group （transfected with si-NC for 24 hours followed by modeling）， si-HAGLR group （transfected with si-HAGLR followed by modeling）， mimic-NC group （transfected with mimic-NC followed by modeling），miR-106b-5p-mimic group （transfected with miR-106b-5p-mimic followed by modeling），and si-HAGLR+miR-106b-5p-mimic group （co-transfected with si-HAGLR and miR-106b-5p-mimic followed by modeling）. Cell proliferation activity was detected by CCK-8 assay. The expressions of lncRNA HAGLR and miR-106b-5p were detected by qRT-PCR. The expressions of IL-1β and IL-18 were detected by immunofluorescence staining and ELISA. The protein expressions of TXNIP，NLRP3，Caspase-1，and GSDMD-N were detected by Western blot.The targeting relationship between lncRNA HAGLR and miR-106b-5p was verified by dual-luciferase reporter gene assay.

Results

Animal experiments： The cartilage injury in the OA model group was more serious than that in the Saline group. Compared with the Saline group， the OA model group exhibited high Mankin score， upregulated expressions of lncRNA HAGLR，TXNIP，NLRP3，Caspase-1，GSDMD-N，IL-1β，and IL-18，and downregulated expression of miR-106b-5p， with all differences being statistically significant （

0.05）. In vitro experiments： compared with the Control group， the OA group exhibited upregulated expressions of lncRNA HAGLR， TXNIP， NLRP3， Caspase-1， GSDMD-N， IL-1β， and IL-18， significantly decreased cell proliferation activity， as well as downregulated expression of miR-106b-5p， with all differences being statistically significant（

0.05）. Compared with the si-NC group， the si-HAGLR group showed significantly downregulated expressions of the aforementioned pyroptosis and inflammation-related indicators， significantly increased cell proliferation activity，along with upregulated expression of miR-106b-5p，with all differences being statistically significant（

0.05）.Compared with the mimic-NC group，the miR-106b-5p-mimic group showed no significant change in lncRNA HAGLR expression （

0.05），but an upregulation in miR-106b-5p expression （

0.05）， increased in ce

ll proliferation activity （

0.05），and downregulation in TXNIP，pyroptosis-related proteins and inflammation-related indicators （

0.05）.The si-HAGLR+ miR-106b-5p-mimic group showed further downregulation of the above pyroptosis and inflammatory indicators and further increase of cell proliferation activity （

0.05）. Dual-luciferase reporter gene assay confirmed the existence of direct binding sites between lncRNA HAGLR and miR-106b-5p.

Conclusion

LncRNA HAGLR promotes TXNIP expression and activates the NLRP3/Caspase-1/GSDMD-N pathway by targeting miR-106b-5p， thereby inducing pyroptosis of OA chondrocytes and exacerbating chondrocyte inflammation and injury.

关键词

Keywords

references

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