Salvianolic acid B activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the KCNQ1OT1/miR-128-3p/SIRT1 signaling pathways
Abstract Purpose Salvianolic acid B (Sal B) possesses strong anti-inflammatory and antioxidant activity. This study aims to explore the underlying mechanism of Sal B to improve the obesity-related osteoarthritis (OA). Methods C57BL/6 J male mice were fed with a normal control diet (NCD), a high fat...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-08-01
|
| Series: | Nutrition & Metabolism |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12986-022-00686-0 |
| _version_ | 1811315446759030784 |
|---|---|
| author | Tianwen Sun Fei Wang Gaojian Hu Zhizhou Li |
| author_facet | Tianwen Sun Fei Wang Gaojian Hu Zhizhou Li |
| author_sort | Tianwen Sun |
| collection | DOAJ |
| description | Abstract Purpose Salvianolic acid B (Sal B) possesses strong anti-inflammatory and antioxidant activity. This study aims to explore the underlying mechanism of Sal B to improve the obesity-related osteoarthritis (OA). Methods C57BL/6 J male mice were fed with a normal control diet (NCD), a high fat diet (HFD), or HFD with Sal B (25 mg/kg), and mouse body weights and osteoarticular inflammatory factor levels were examined. Mouse chondrogenic cell line ATDC5 were transfected with lncRNA KCNQ1 overlapping transcript 1 small hairpin RNA (KCNQ1OT1 shRNA), miR-128-3p mimic or Sirtuin-1 small interfering RNA (SIRT1 siRNA), then stimulated with Palmitic acid (PA) followed by the treatment of Sal B. Then, inflammatory response, apoptosis, and autophagy of ATDC5 cells in different groups were detected. Results Sal B reduced the body weight, decreased the levels of inflammatory markers, and improved cartilage damage in OA mice fed with HFD. KCNQ1OT1 was downregulated in OA mice fed with HFD, and PA-stimulated ATDC5 cells. Sal B protected ATDC5 cells against PA-mediated inflammation, apoptosis, and the inhibition of autophagy, while knockdown of KCNQ1OT1 reversed these results. KCNQ1OT1 was found to be functioned as a ceRNA to bind and downregulate the expression of miR-128-3p that was upregulated in PA-induced cells. Furthermore, SIRT1 was verified as a target of miR-128-3p. MiR-128-3p overexpression reversed the effects of Sal B on inflammatory response, apoptosis, and autophagy in PA-stimulated cells, and knockdown of SIRT1 displayed the similar results. Conclusion Sal B exerted a chondroprotective effect by upregulating KCNQ1OT1, which indicates Sal B can used for a therapeutic agent in obesity-related OA. |
| first_indexed | 2024-04-13T11:30:26Z |
| format | Article |
| id | doaj.art-11049a3aa426443fb098a2c20b0513ed |
| institution | Directory Open Access Journal |
| issn | 1743-7075 |
| language | English |
| last_indexed | 2024-04-13T11:30:26Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Nutrition & Metabolism |
| spelling | doaj.art-11049a3aa426443fb098a2c20b0513ed2022-12-22T02:48:35ZengBMCNutrition & Metabolism1743-70752022-08-0119111710.1186/s12986-022-00686-0Salvianolic acid B activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the KCNQ1OT1/miR-128-3p/SIRT1 signaling pathwaysTianwen Sun0Fei Wang1Gaojian Hu2Zhizhou Li3Department of Orthopedics, China-Japan Union Hospital of Jilin UniversityDepartment of Orthopedics, China-Japan Union Hospital of Jilin UniversityDepartment of Orthopedics, China-Japan Union Hospital of Jilin UniversityDepartment of Orthopedics, China-Japan Union Hospital of Jilin UniversityAbstract Purpose Salvianolic acid B (Sal B) possesses strong anti-inflammatory and antioxidant activity. This study aims to explore the underlying mechanism of Sal B to improve the obesity-related osteoarthritis (OA). Methods C57BL/6 J male mice were fed with a normal control diet (NCD), a high fat diet (HFD), or HFD with Sal B (25 mg/kg), and mouse body weights and osteoarticular inflammatory factor levels were examined. Mouse chondrogenic cell line ATDC5 were transfected with lncRNA KCNQ1 overlapping transcript 1 small hairpin RNA (KCNQ1OT1 shRNA), miR-128-3p mimic or Sirtuin-1 small interfering RNA (SIRT1 siRNA), then stimulated with Palmitic acid (PA) followed by the treatment of Sal B. Then, inflammatory response, apoptosis, and autophagy of ATDC5 cells in different groups were detected. Results Sal B reduced the body weight, decreased the levels of inflammatory markers, and improved cartilage damage in OA mice fed with HFD. KCNQ1OT1 was downregulated in OA mice fed with HFD, and PA-stimulated ATDC5 cells. Sal B protected ATDC5 cells against PA-mediated inflammation, apoptosis, and the inhibition of autophagy, while knockdown of KCNQ1OT1 reversed these results. KCNQ1OT1 was found to be functioned as a ceRNA to bind and downregulate the expression of miR-128-3p that was upregulated in PA-induced cells. Furthermore, SIRT1 was verified as a target of miR-128-3p. MiR-128-3p overexpression reversed the effects of Sal B on inflammatory response, apoptosis, and autophagy in PA-stimulated cells, and knockdown of SIRT1 displayed the similar results. Conclusion Sal B exerted a chondroprotective effect by upregulating KCNQ1OT1, which indicates Sal B can used for a therapeutic agent in obesity-related OA.https://doi.org/10.1186/s12986-022-00686-0Salvianolic acid BKCNQ1OT1ObesityAutophagyOsteoarthritis |
| spellingShingle | Tianwen Sun Fei Wang Gaojian Hu Zhizhou Li Salvianolic acid B activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the KCNQ1OT1/miR-128-3p/SIRT1 signaling pathways Nutrition & Metabolism Salvianolic acid B KCNQ1OT1 Obesity Autophagy Osteoarthritis |
| title | Salvianolic acid B activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the KCNQ1OT1/miR-128-3p/SIRT1 signaling pathways |
| title_full | Salvianolic acid B activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the KCNQ1OT1/miR-128-3p/SIRT1 signaling pathways |
| title_fullStr | Salvianolic acid B activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the KCNQ1OT1/miR-128-3p/SIRT1 signaling pathways |
| title_full_unstemmed | Salvianolic acid B activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the KCNQ1OT1/miR-128-3p/SIRT1 signaling pathways |
| title_short | Salvianolic acid B activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the KCNQ1OT1/miR-128-3p/SIRT1 signaling pathways |
| title_sort | salvianolic acid b activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the kcnq1ot1 mir 128 3p sirt1 signaling pathways |
| topic | Salvianolic acid B KCNQ1OT1 Obesity Autophagy Osteoarthritis |
| url | https://doi.org/10.1186/s12986-022-00686-0 |
| work_keys_str_mv | AT tianwensun salvianolicacidbactivateschondrocytesautophagyandreduceschondrocyteapoptosisinobesemiceviathekcnq1ot1mir1283psirt1signalingpathways AT feiwang salvianolicacidbactivateschondrocytesautophagyandreduceschondrocyteapoptosisinobesemiceviathekcnq1ot1mir1283psirt1signalingpathways AT gaojianhu salvianolicacidbactivateschondrocytesautophagyandreduceschondrocyteapoptosisinobesemiceviathekcnq1ot1mir1283psirt1signalingpathways AT zhizhouli salvianolicacidbactivateschondrocytesautophagyandreduceschondrocyteapoptosisinobesemiceviathekcnq1ot1mir1283psirt1signalingpathways |