Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro
Abstract Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SF) play a major role in cartilage and bone destruction through tumorlike proliferation, migration, and invasion. Nesfatin-1, an 82-amino-acid-long peptide discovered by Oh-I in 2006, is derived from the...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-12-01
|
| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-022-03453-2 |
| _version_ | 1797973545998876672 |
|---|---|
| author | Shuo Zhang Tao Zhang Yayun Xu Genxiang Rong Juehua Jing |
| author_facet | Shuo Zhang Tao Zhang Yayun Xu Genxiang Rong Juehua Jing |
| author_sort | Shuo Zhang |
| collection | DOAJ |
| description | Abstract Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SF) play a major role in cartilage and bone destruction through tumorlike proliferation, migration, and invasion. Nesfatin-1, an 82-amino-acid-long peptide discovered by Oh-I in 2006, is derived from the precursor protein nucleobindin-2 (NUCB2). NUCB2/nesfatin-1 promotes cell proliferation, migration, and invasion in various tumors. We have previously shown that increased nesfatin-1 levels in the synovium may be associated with disease severity in patients with RA. However, the effect of NUCB2 on the tumorlike transformation of RASF has not yet been reported. The expression of NUCB2 mRNA in the synovium of RA and non-RA patients was further confirmed using three individual datasets from the NCBI GEO database. Gene set enrichment analysis (GSEA) was employed to explore the association between NUCB2 mRNA and RA-related gene signatures or signaling pathways in the GSE77298 dataset. Cell proliferation, migration, and invasion abilities were determined using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), wound healing, and transwell assays, respectively. The results showed that the levels of NUCB2 mRNA in the synovium were significantly elevated in patients with RA. Moreover, GSEA showed that high expression of NUCB2 mRNA was related to gene signatures, including those involved in the cell cycle, DNA replication, extracellular matrix–receptor interaction, and focal adhesion. Furthermore, the results of CCK-8 and EdU assays indicated that inhibition of NUCB2 markedly repressed RASF proliferation. Additionally, the results of wound healing and transwell assays demonstrated that inhibition of NUCB2 significantly suppressed the migratory and invasive abilities of RASFs. Our findings are the first to demonstrate that the inhibition of NUCB2 suppresses the proliferation, migration, and invasion of RASFs in vitro. |
| first_indexed | 2024-04-11T04:05:58Z |
| format | Article |
| id | doaj.art-1a57b6a1458945e9a9b59b3e9b338f61 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-11T04:05:58Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-1a57b6a1458945e9a9b59b3e9b338f612023-01-01T12:23:09ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2022-12-0117111010.1186/s13018-022-03453-2Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitroShuo Zhang0Tao Zhang1Yayun Xu2Genxiang Rong3Juehua Jing4Department of Orthopedics, The Second Affiliated Hospital of Anhui Medical UniversityInflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical UniversityInflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Anhui Medical UniversityAbstract Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SF) play a major role in cartilage and bone destruction through tumorlike proliferation, migration, and invasion. Nesfatin-1, an 82-amino-acid-long peptide discovered by Oh-I in 2006, is derived from the precursor protein nucleobindin-2 (NUCB2). NUCB2/nesfatin-1 promotes cell proliferation, migration, and invasion in various tumors. We have previously shown that increased nesfatin-1 levels in the synovium may be associated with disease severity in patients with RA. However, the effect of NUCB2 on the tumorlike transformation of RASF has not yet been reported. The expression of NUCB2 mRNA in the synovium of RA and non-RA patients was further confirmed using three individual datasets from the NCBI GEO database. Gene set enrichment analysis (GSEA) was employed to explore the association between NUCB2 mRNA and RA-related gene signatures or signaling pathways in the GSE77298 dataset. Cell proliferation, migration, and invasion abilities were determined using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), wound healing, and transwell assays, respectively. The results showed that the levels of NUCB2 mRNA in the synovium were significantly elevated in patients with RA. Moreover, GSEA showed that high expression of NUCB2 mRNA was related to gene signatures, including those involved in the cell cycle, DNA replication, extracellular matrix–receptor interaction, and focal adhesion. Furthermore, the results of CCK-8 and EdU assays indicated that inhibition of NUCB2 markedly repressed RASF proliferation. Additionally, the results of wound healing and transwell assays demonstrated that inhibition of NUCB2 significantly suppressed the migratory and invasive abilities of RASFs. Our findings are the first to demonstrate that the inhibition of NUCB2 suppresses the proliferation, migration, and invasion of RASFs in vitro.https://doi.org/10.1186/s13018-022-03453-2Rheumatoid arthritisSynovial fibroblastNucleobindin-2SynoviumProliferationMigration |
| spellingShingle | Shuo Zhang Tao Zhang Yayun Xu Genxiang Rong Juehua Jing Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro Journal of Orthopaedic Surgery and Research Rheumatoid arthritis Synovial fibroblast Nucleobindin-2 Synovium Proliferation Migration |
| title | Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro |
| title_full | Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro |
| title_fullStr | Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro |
| title_full_unstemmed | Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro |
| title_short | Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro |
| title_sort | inhibition of nucb2 suppresses the proliferation migration and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro |
| topic | Rheumatoid arthritis Synovial fibroblast Nucleobindin-2 Synovium Proliferation Migration |
| url | https://doi.org/10.1186/s13018-022-03453-2 |
| work_keys_str_mv | AT shuozhang inhibitionofnucb2suppressestheproliferationmigrationandinvasionofrheumatoidarthritissynovialfibroblastsfrompatientswithrheumatoidarthritisinvitro AT taozhang inhibitionofnucb2suppressestheproliferationmigrationandinvasionofrheumatoidarthritissynovialfibroblastsfrompatientswithrheumatoidarthritisinvitro AT yayunxu inhibitionofnucb2suppressestheproliferationmigrationandinvasionofrheumatoidarthritissynovialfibroblastsfrompatientswithrheumatoidarthritisinvitro AT genxiangrong inhibitionofnucb2suppressestheproliferationmigrationandinvasionofrheumatoidarthritissynovialfibroblastsfrompatientswithrheumatoidarthritisinvitro AT juehuajing inhibitionofnucb2suppressestheproliferationmigrationandinvasionofrheumatoidarthritissynovialfibroblastsfrompatientswithrheumatoidarthritisinvitro |