Mechanism of curcumin alleviating secondary cartilage damage by inhibiting lncRNA ARFRP1

SHI Guirong; REN Bowen; ZHANG Zhongbo; WANG Lisha; ZHANG Qiwei; SHI Dongliang

doi:10.14188/j.1671-8852.2024.0119

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Mechanism of curcumin alleviating secondary cartilage damage by inhibiting lncRNA ARFRP1

更新时间：2026-11-05

- Mechanism of curcumin alleviating secondary cartilage damage by inhibiting lncRNA ARFRP1
- Medical Journal of Wuhan University Vol. 46, Issue 4, Pages: 446-455(2025)
- 作者机构：
  
  1.商丘医学高等专科学校临床医学院中医教研室河南商丘 476000
  2.河南省中医院骨病一科河南郑州 450000
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0119
  CLC： R274.12
- Received：21 February 2024，
  
  Published：25 April 2025
- 稿件说明：
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史桂荣,任博文,张仲博等.姜黄素通过抑制lncRNA ARFRP1缓解继发性软骨损伤的机制[J].武汉大学学报（医学版）,2025,46(04):446-455.

SHI Guirong,REN Bowen,ZHANG Zhongbo,et al.Mechanism of curcumin alleviating secondary cartilage damage by inhibiting lncRNA ARFRP1[J].Medical Journal of Wuhan University,2025,46(04):446-455.
史桂荣,任博文,张仲博等.姜黄素通过抑制lncRNA ARFRP1缓解继发性软骨损伤的机制[J].武汉大学学报（医学版）,2025,46(04):446-455. DOI： 10.14188/j.1671-8852.2024.0119.

SHI Guirong,REN Bowen,ZHANG Zhongbo,et al.Mechanism of curcumin alleviating secondary cartilage damage by inhibiting lncRNA ARFRP1[J].Medical Journal of Wuhan University,2025,46(04):446-455. DOI： 10.14188/j.1671-8852.2024.0119.

摘要

目的

探讨姜黄素对大鼠继发性软骨损伤的影响。

方法

将SD大鼠随机分为假手术组、软骨损伤模型组、50 mg

⋅kg

-1

姜黄素组、100 mg⋅kg

-1

姜黄素组，每组10只大鼠。建立继发性软骨损伤大鼠模型，给予不同剂量姜黄素（50、100 mg⋅kg

-1

）干预。给药10周后，切取软骨组织进行番红O⁃固绿染色，采用OARSI关节病理评分评价染色结果。体外分离培养软骨细胞，姜黄素对软骨细胞的毒性采用CCK⁃8实验进行评估。分别用浓度为10、40 μmol⋅L

-1

的姜黄素预先处理细胞24 h，随后用10 μg⋅L

-1

的IL⁃1β刺激细胞24 h。构建长链非编码RNA ADP⁃核糖基化因子相关蛋白1（lncRNA ARFRP1）过表达载体转染细胞。采用流式细胞仪检测细胞凋亡能力，酶联免疫吸附实验（ELISA）检测炎症因子水平，实时荧光定量⁃PCR（RT⁃qPCR）检测ARFRP1表达，蛋白质印记法（Western Blot）检测Ⅱ型胶原（Collagen Ⅱ）、凋亡蛋白（Caspase3、Caspase9）和JNK/MAPK通路相关蛋白（p⁃JNK、p⁃p38）的表达。

结果

100 mg⋅kg

-1

姜黄素治疗组OARSI评分为3.03，较模型组7.38明显降低。此外，姜黄素呈剂量依赖性促进软骨细胞增殖，降低IL⁃1β诱导的细胞凋亡和炎症因子分泌，以及Collagen Ⅱ、凋亡蛋白以及JNK通路蛋白表达。过表达lncRNA ARFRP1或JNK通路激活剂茴香霉素（Anisomycin）处理能抑制姜黄素对软骨细胞的保护作用。

结论

姜黄素通过抑制lncRNA⁃ARFRP1表达缓解继发性大鼠软骨损伤。

Abstract

Objective

To investigate the effect of curcumin on secondary cartilage damage in rats.

Methods

SD rats were randomly divided into the sham operation group

cartilage injury model group

50 mg⋅kg

-1

curcumin group

and 100 mg⋅kg

-1

curcumin group

with 10 rats in each group. A rat model of secondary cartilage damage was established

different concentrations of curcumin (50

100 mg⋅kg

-1

) were administered for intervention

and after 10 weeks of administration

cartilage tissues were excised for safranin O⁃fast green staining

and the staining results were evaluated by the osteoarthritis research society international （OARSI） joint pathology score. Chondrocytes were isolated and cultured

in vitro

and the toxicity of curcumin on chondrocytes was evaluated by using the cell counting kit⁃8 (CCK⁃8) assay. Cells were pretreated with curcumin at concentrations of 10 and 40 μmol⋅L

-1

for 24 h and subsequently stimulated with IL⁃1β for 24 h. Long noncoding RNA ADP ribosylation factor⁃related protein 1 (lncRNA ARFRP1) overexpression vectors were constructed and transfected in

to cells. Cell apoptosis was assessed by flow cytometry

levels of inflammatory factors were assessed by enzyme⁃linked immunosorbent assay (ELISA)

ARFRP1 expression was assessed by real⁃time quantitative PCR (RT qPCR)

and protein levels of collagen type Ⅱ (CollagenⅡ)

apoptotic proteins (Caspase3 and caspase9) and JNK/MAPK pathway⁃related proteins (p⁃JNK

p⁃p38) were assessed by Western Blot.

Results

The OARSI score of rats in the 100 mg⋅kg

-1

curcumin treatment group was 3.03

which was significantly lower than the score of 7.38 in the model group. Curcumin dose⁃dependently promoted the proliferation of chondrocytes and reduced IL⁃1β⁃induced apoptosis

expression levels of inflammatory factors

collagen Ⅱ

apoptotic proteins

as well as pathway proteins. Moreover

overexpression of lncRNA ARFRP1 or anisomycin

an activator of JNK

was able to inhibit the protective effect of curcumin on chondrocytes.

Conclusion

Curcumin alleviates secondary rat cartilage damage by inhibiting lncRNA ARFRP1 expression.

关键词

Keywords

references

SHIH P C , LEE Y H , TSOU H K , et al . Recent targets of osteoarthritis research [J ] . Best Pract Res Clin Rheumatol , 2023 , 37 ( 2 ): 101851 .

MOBASHERI A , THUDIUM C S , BAY⁃JENSEN A C , et al . Biomarkers for osteoarthritis: Current status and future prospects [J ] . Best Pract Res Clin Rheumatol , 2023 , 37 ( 2 ): 101852 .

LESTARI M L , INDRAYANTO G . Curcumin [J ] . Profiles Drug Subst Excip Relat Methodol , 2014 , 39 : 113 ⁃ 204 .

FENG K , GE Y , CHEN Z , et al . Curcumin inhibits the PERK⁃eIF2α⁃CHOP pathway through promoting SIRT1 expression in oxidative stress⁃induced rat chondrocytes and ameliorates osteoarthritis progression in a rat model [J ] . Oxid Med Cell Longev , 2019 , 2019 : 8574386 .

PAULTRE K , CADE W , HERNANDEZ D , et al . Therapeutic effects of turmeric or curcumin extract on pain and function for individuals with knee osteoarthritis: A systematic review [ J ] . BMJ Open Sport Exerc Med , 2021 , 7 ( 1 ): e000935 .

PANKNIN T M , HOWE C L , HAUER M , et al . Curcumin supplementation and human disease: A scoping review of clinical trials [J ] . Int J Mol Sci , 2023 , 24 ( 5 ): 4476 .

ZHANG G , ZHANG Q , ZHU J , et al . LncRNA ARFRP1 knockdown inhibits LPS⁃induced the injury of chondrocytes by regulation of NF⁃κB pathway through modulating miR⁃15a⁃5p/TLR4 axis [J ] . Life Sci , 2020 , 261 : 118429 .

XIAO Y , YAN X , YANG Y , et al . Downregulation of long noncoding RNA HOTAIRM1 variant 1 contributes to osteoarthritis via regulating miR⁃125b/BMPR2 axis and activating JNK/MAPK/ERK pathway [J ] . Biomed Pharmacother , 2019 , 109 : 1569 ⁃ 1577 .

YU H , LI M , WEN X , et al . Elevation of α⁃1,3 fucosylation promotes the binding ability of TNFR1 to TNF⁃α and contributes to osteoarthritic cartilage destruction and apoptosis [J ] . Arthritis Res Ther , 2022 , 24 ( 1 ): 93 .

ZHOU Y , MING J , DENG M , et al . Chemically modified curcumin (CMC2.24) alleviates osteoarthritis progression by restoring cartilage homeostasis and inhibiting chondrocyte apoptosis via the NF⁃κB/HIF⁃2α axis [J ] . J Mol Med (Berl) , 2020 , 98 ( 10 ): 1479 ⁃ 1491 .

JIANG C , LUO P , LI X , et al . Nrf2/ARE is a key pathway for curcumin⁃mediated protection of TMJ chondrocytes from oxidative stress and inflammation [J ] . Cell Stress Chaperones , 2020 , 25 ( 3 ): 395 ⁃ 406 .

PARK S , LEE L R , SEO J H , et al . Curcumin and tetrahydrocurcumin both prevent osteoarthritis symptoms and decrease the expressions of pro⁃inflammatory cytokines in estrogen⁃deficient rats [J ] . Genes Nutr , 2016 , 11 : 2 .

ZHANG L , ZHANG H , XIE Q , et al . LncRNA⁃mediated cartilage homeostasis in osteoarthritis: A narrative review [J ] . Front Med (Lausanne) , 2024 , 11 : 1326843 .

ZHANG X , LIU Q , ZHANG J , et al . The emerging role of lncRNAs in osteoarthritis development and potential therapy [J ] . Front Genet , 2023 , 14 : 1273933 .

YU H , XIE Y , ZHOU Z , et al . Curcumin regulates the progression of colorectal cancer via LncRNA NBR2/AMPK pathway [J ] . Technol Cancer Res Treat , 2019 , 18 : 1533033819870781 .

HUANG W , LI X , WANG D , et al . Curcumin reduces LPS⁃induced septic acute kidney injury through suppression of lncRNA PVT1 in mice [J ] . Life Sci , 2020 , 254 : 117340 .

GE H X , ZOU F M , LI Y , et al . JNK pathway in osteoarthritis: Pathological and therapeutic aspects [J ] . J Recept Signal Transduct Res , 2017 , 37 ( 5 ): 431 ⁃ 436 .

LI H , WANG Q , GONG D . LINC00313 alleviates osteoarthritis progression in mice through promoting TRAF1 promoter methylation and inhibiting the ASK1/JNK signaling pathway [J ] . Immunopharmacol Immunotoxicol , 2022 , 44 ( 5 ): 732 ⁃ 745 .

XU Y , GU Y , JI W , et al . Activation of the extracellular⁃signal⁃regulated kinase (ERK)/c⁃Jun N⁃terminal kinase (JNK) signal pathway and osteogenic factors in subchondral bone of patients with knee osteoarthritis [J ] . Ann Transl Med , 2021 , 9 ( 8 ): 663 .

PANG Y , ZHAO L , JI X , et al . Analyses of transcriptomics upon IL⁃1β⁃stimulated mouse chondrocytes and the protective effect of catalpol through the NOD2/NF⁃κB/MAPK signaling pathway [J ] . Molecules , 2023 , 28 ( 4 ): 1606 .

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