Secretory phosphoprotein 1 secreted by fibroblast-like synoviocytes promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis
Synovial tissue hyperplasia is a major cause of bone damage in rheumatoid arthritis (RA). Over-proliferation and secretion of cytokines of fibroblast-like synoviocytes (FLSs) are key contributors to bone damage in the joint microenvironment. Therefore, inhibition of FLSs-mediated bone damage is of g...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222010769 |
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| author | Xiaoyu Cai Yan Zheng Fujia Ren Shiwei Zhang Linwen Wu Yao Yao |
| author_facet | Xiaoyu Cai Yan Zheng Fujia Ren Shiwei Zhang Linwen Wu Yao Yao |
| author_sort | Xiaoyu Cai |
| collection | DOAJ |
| description | Synovial tissue hyperplasia is a major cause of bone damage in rheumatoid arthritis (RA). Over-proliferation and secretion of cytokines of fibroblast-like synoviocytes (FLSs) are key contributors to bone damage in the joint microenvironment. Therefore, inhibition of FLSs-mediated bone damage is of great significance in RA patients. The aim of this study was to investigate the molecular mechanisms by which FLSs-mediated bone damage in the joint microenvironment. The results of whole transcriptome sequencing showed that Spp1 gene expression was significantly upregulated in collagen-induced arthritis FLSs compared to Normal FLSs. KEGG enrichment analysis revealed up-regulated Spp1 gene expression, associated with PI3K/AKT signaling. Animal and cellular experiments were designed to validate and explore the results of sequencing. Briefly, the data demonstrated secretory phosphoprotein 1 (SPP1) (encoded by Spp1 gene) secreted by FLSs promotes osteoclasts differentiation in vivo and in vitro and exacerbates articular bone damage in collagen-induced arthritis mice. Interestingly, SPP1 secreted by FLSs does not affect its own proliferation and apoptosis. The results of co-culture of FLSs with bone marrow-derived monocytes indicated the level of SPP1 secreted by FLSs positively correlates with the frequency of p-PI3K+PI3K+ osteoclasts, whereas not with the frequency of p-AKT+AKT+ osteoclasts. This may suggest that SPP1 secreted by FLSs acts directly on PI3K while indirectly on AKT. Together, the results revealed SPP1 secreted by FLSs promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis. Regulation of Spp1 gene expression in FLSs may be a potential approach to treat RA bone damage in the joint microenvironment. |
| first_indexed | 2024-04-11T19:49:33Z |
| format | Article |
| id | doaj.art-b368f948fd944bf7849994edc29e9a65 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-11T19:49:33Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-b368f948fd944bf7849994edc29e9a652022-12-22T04:06:21ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-11-01155113687Secretory phosphoprotein 1 secreted by fibroblast-like synoviocytes promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritisXiaoyu Cai0Yan Zheng1Fujia Ren2Shiwei Zhang3Linwen Wu4Yao Yao5Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Geriatrics, Zhejiang Provincial People’s Hospital, Hangzhou, ChinaDepartment of Pharmacy, Hangzhou Women’s Hospital, Hangzhou, ChinaDepartment of Anesthesiology, The First Afriiated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou 310006, China; Corresponding authors.Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Corresponding authors.Synovial tissue hyperplasia is a major cause of bone damage in rheumatoid arthritis (RA). Over-proliferation and secretion of cytokines of fibroblast-like synoviocytes (FLSs) are key contributors to bone damage in the joint microenvironment. Therefore, inhibition of FLSs-mediated bone damage is of great significance in RA patients. The aim of this study was to investigate the molecular mechanisms by which FLSs-mediated bone damage in the joint microenvironment. The results of whole transcriptome sequencing showed that Spp1 gene expression was significantly upregulated in collagen-induced arthritis FLSs compared to Normal FLSs. KEGG enrichment analysis revealed up-regulated Spp1 gene expression, associated with PI3K/AKT signaling. Animal and cellular experiments were designed to validate and explore the results of sequencing. Briefly, the data demonstrated secretory phosphoprotein 1 (SPP1) (encoded by Spp1 gene) secreted by FLSs promotes osteoclasts differentiation in vivo and in vitro and exacerbates articular bone damage in collagen-induced arthritis mice. Interestingly, SPP1 secreted by FLSs does not affect its own proliferation and apoptosis. The results of co-culture of FLSs with bone marrow-derived monocytes indicated the level of SPP1 secreted by FLSs positively correlates with the frequency of p-PI3K+PI3K+ osteoclasts, whereas not with the frequency of p-AKT+AKT+ osteoclasts. This may suggest that SPP1 secreted by FLSs acts directly on PI3K while indirectly on AKT. Together, the results revealed SPP1 secreted by FLSs promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis. Regulation of Spp1 gene expression in FLSs may be a potential approach to treat RA bone damage in the joint microenvironment.http://www.sciencedirect.com/science/article/pii/S0753332222010769SPP1Rheumatoid arthritisFLSsOsteoclastsSequencingBone damage |
| spellingShingle | Xiaoyu Cai Yan Zheng Fujia Ren Shiwei Zhang Linwen Wu Yao Yao Secretory phosphoprotein 1 secreted by fibroblast-like synoviocytes promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis Biomedicine & Pharmacotherapy SPP1 Rheumatoid arthritis FLSs Osteoclasts Sequencing Bone damage |
| title | Secretory phosphoprotein 1 secreted by fibroblast-like synoviocytes promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis |
| title_full | Secretory phosphoprotein 1 secreted by fibroblast-like synoviocytes promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis |
| title_fullStr | Secretory phosphoprotein 1 secreted by fibroblast-like synoviocytes promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis |
| title_full_unstemmed | Secretory phosphoprotein 1 secreted by fibroblast-like synoviocytes promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis |
| title_short | Secretory phosphoprotein 1 secreted by fibroblast-like synoviocytes promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis |
| title_sort | secretory phosphoprotein 1 secreted by fibroblast like synoviocytes promotes osteoclasts formation via pi3k akt signaling in collagen induced arthritis |
| topic | SPP1 Rheumatoid arthritis FLSs Osteoclasts Sequencing Bone damage |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222010769 |
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