LncRNA PTS-1 Protects Against Osteoarthritis Through the miR-8085/E2F2 Axis
Cheng Ma,1,* Qi Chen,2,* Yi-Fan Wei,1,* Shu-Wen Chen,3 Huan Liu,4 Feng Xin,5 Yong-Xin Ren1 1Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Orthopaedics, The Affiliated Chang...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-01-01
|
| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/lncrna-pts-1-protects-against-osteoarthritis-through-the-mir-8085e2f2--peer-reviewed-fulltext-article-JIR |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841551099618656256 |
|---|---|
| author | Ma C Chen Q Wei YF Chen SW Liu H Xin F Ren YX |
| author_facet | Ma C Chen Q Wei YF Chen SW Liu H Xin F Ren YX |
| author_sort | Ma C |
| collection | DOAJ |
| description | Cheng Ma,1,* Qi Chen,2,* Yi-Fan Wei,1,* Shu-Wen Chen,3 Huan Liu,4 Feng Xin,5 Yong-Xin Ren1 1Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Orthopaedics, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 3Department of Clinical College, The First Clinical School of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Orthopaedics, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China; 5Department of Orthopaedics, Xuzhou Cancer Hospital, Xuzhou, Jiangsu, 221005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Xin; Yong-Xin Ren, Email 925866554@qq.com; renyongxinjsph@163.comBackground: Osteoarthritis (OA) is a leading cause of pain, disability, and reduced mobility worldwide, characterized by metabolic imbalances in chondrocytes, extracellular matrix (ECM), and subchondral bone. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in OA pathogenesis. This study focuses on lncRNA PTS-1, a novel lncRNA, to explore its function and regulatory mechanisms in OA progression.Methods: The expression profile of lncRNAs was assessed using RNA sequencing and qRT-PCR. The expression of lnc-PTS-1 was further validated by qRT-PCR in degenerated cartilage tissues, degenerative primary chondrocytes, and IL-1β-treated C28/I2 cells. Cell viability, proliferation, and apoptosis rates, along with the mRNA and protein levels of apoptosis-related markers (cleaved Caspase 3, cleaved Caspase 9, Bcl-2, Bax), ECM metabolism markers (MMP-3, MMP-13, aggrecan, collagen II), and inflammation-related markers (IL-1β, IL-6, TNF-α) were evaluated using Cell Counting Kit-8, Toluidine Blue staining, Alcian Blue staining, flow cytometry, qRT-PCR, immunofluorescence, and Western Blot. The interaction between miR-8085 and lnc-PTS-1 or E2F2 was investigated through dual luciferase reporter assays and RNA immunoprecipitation (RIP) analyses.Results: Lnc-PTS-1 expression was significantly downregulated in degenerated cartilage tissues, IL-1β-induced degenerative primary chondrocytes and C28/I2 cells. Functional experiments showed that lnc-PTS-1 knockdown aggravated IL-1β-induced ECM degradation, chondrocyte apoptosis, and inflammation, while its overexpression provided protective effects. Mechanistically, lnc-PTS-1 acted as a competing endogenous RNA (ceRNA) by sponging miR-8085, thereby upregulating E2F2 expression. Notably, miR-8085 upregulation diminished the protective effects of lnc-PTS-1 on ECM degradation, apoptosis, and inflammation, while E2F2 upregulation partially alleviated IL-1β-induced damage. However, these mitigating effects were reversed by miR-8085 overexpression.Conclusion: These findings identify lnc-PTS-1/miR-8085/E2F2 axis as a novel regulatory mechanism in OA pathogenesis, providing theoretical basis and experimental evidence for the potential clinical application of new lncRNA molecules in the treatment of OA.Keywords: osteoarthritis, long non-coding RNA PTS-1, E2F2, miR-8085 |
| format | Article |
| id | doaj-art-d2f36cde96f6486299cf816fd25019d0 |
| institution | Kabale University |
| issn | 1178-7031 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj-art-d2f36cde96f6486299cf816fd25019d02025-01-09T16:58:34ZengDove Medical PressJournal of Inflammation Research1178-70312025-01-01Volume 1834736699079LncRNA PTS-1 Protects Against Osteoarthritis Through the miR-8085/E2F2 AxisMa CChen QWei YFChen SWLiu HXin FRen YXCheng Ma,1,* Qi Chen,2,* Yi-Fan Wei,1,* Shu-Wen Chen,3 Huan Liu,4 Feng Xin,5 Yong-Xin Ren1 1Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Orthopaedics, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 3Department of Clinical College, The First Clinical School of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Orthopaedics, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China; 5Department of Orthopaedics, Xuzhou Cancer Hospital, Xuzhou, Jiangsu, 221005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Xin; Yong-Xin Ren, Email 925866554@qq.com; renyongxinjsph@163.comBackground: Osteoarthritis (OA) is a leading cause of pain, disability, and reduced mobility worldwide, characterized by metabolic imbalances in chondrocytes, extracellular matrix (ECM), and subchondral bone. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in OA pathogenesis. This study focuses on lncRNA PTS-1, a novel lncRNA, to explore its function and regulatory mechanisms in OA progression.Methods: The expression profile of lncRNAs was assessed using RNA sequencing and qRT-PCR. The expression of lnc-PTS-1 was further validated by qRT-PCR in degenerated cartilage tissues, degenerative primary chondrocytes, and IL-1β-treated C28/I2 cells. Cell viability, proliferation, and apoptosis rates, along with the mRNA and protein levels of apoptosis-related markers (cleaved Caspase 3, cleaved Caspase 9, Bcl-2, Bax), ECM metabolism markers (MMP-3, MMP-13, aggrecan, collagen II), and inflammation-related markers (IL-1β, IL-6, TNF-α) were evaluated using Cell Counting Kit-8, Toluidine Blue staining, Alcian Blue staining, flow cytometry, qRT-PCR, immunofluorescence, and Western Blot. The interaction between miR-8085 and lnc-PTS-1 or E2F2 was investigated through dual luciferase reporter assays and RNA immunoprecipitation (RIP) analyses.Results: Lnc-PTS-1 expression was significantly downregulated in degenerated cartilage tissues, IL-1β-induced degenerative primary chondrocytes and C28/I2 cells. Functional experiments showed that lnc-PTS-1 knockdown aggravated IL-1β-induced ECM degradation, chondrocyte apoptosis, and inflammation, while its overexpression provided protective effects. Mechanistically, lnc-PTS-1 acted as a competing endogenous RNA (ceRNA) by sponging miR-8085, thereby upregulating E2F2 expression. Notably, miR-8085 upregulation diminished the protective effects of lnc-PTS-1 on ECM degradation, apoptosis, and inflammation, while E2F2 upregulation partially alleviated IL-1β-induced damage. However, these mitigating effects were reversed by miR-8085 overexpression.Conclusion: These findings identify lnc-PTS-1/miR-8085/E2F2 axis as a novel regulatory mechanism in OA pathogenesis, providing theoretical basis and experimental evidence for the potential clinical application of new lncRNA molecules in the treatment of OA.Keywords: osteoarthritis, long non-coding RNA PTS-1, E2F2, miR-8085https://www.dovepress.com/lncrna-pts-1-protects-against-osteoarthritis-through-the-mir-8085e2f2--peer-reviewed-fulltext-article-JIRosteoarthritislong non-coding rna pts-1e2f2mir-8085 |
| spellingShingle | Ma C Chen Q Wei YF Chen SW Liu H Xin F Ren YX LncRNA PTS-1 Protects Against Osteoarthritis Through the miR-8085/E2F2 Axis Journal of Inflammation Research osteoarthritis long non-coding rna pts-1 e2f2 mir-8085 |
| title | LncRNA PTS-1 Protects Against Osteoarthritis Through the miR-8085/E2F2 Axis |
| title_full | LncRNA PTS-1 Protects Against Osteoarthritis Through the miR-8085/E2F2 Axis |
| title_fullStr | LncRNA PTS-1 Protects Against Osteoarthritis Through the miR-8085/E2F2 Axis |
| title_full_unstemmed | LncRNA PTS-1 Protects Against Osteoarthritis Through the miR-8085/E2F2 Axis |
| title_short | LncRNA PTS-1 Protects Against Osteoarthritis Through the miR-8085/E2F2 Axis |
| title_sort | lncrna pts 1 protects against osteoarthritis through the mir 8085 e2f2 axis |
| topic | osteoarthritis long non-coding rna pts-1 e2f2 mir-8085 |
| url | https://www.dovepress.com/lncrna-pts-1-protects-against-osteoarthritis-through-the-mir-8085e2f2--peer-reviewed-fulltext-article-JIR |
| work_keys_str_mv | AT mac lncrnapts1protectsagainstosteoarthritisthroughthemir8085e2f2axis AT chenq lncrnapts1protectsagainstosteoarthritisthroughthemir8085e2f2axis AT weiyf lncrnapts1protectsagainstosteoarthritisthroughthemir8085e2f2axis AT chensw lncrnapts1protectsagainstosteoarthritisthroughthemir8085e2f2axis AT liuh lncrnapts1protectsagainstosteoarthritisthroughthemir8085e2f2axis AT xinf lncrnapts1protectsagainstosteoarthritisthroughthemir8085e2f2axis AT renyx lncrnapts1protectsagainstosteoarthritisthroughthemir8085e2f2axis |