Rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loop
Abstract Fibroblast-like synoviocytes (FLSs) and osteoclasts are central cells in the maintenance of joint homeostasis. Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints that induces cytokine-activated FLSs and progressive bone erosion. Interactions between FLSs and other cells,...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-02-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-025-01401-8 |
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| author | Eun Sun Lee Hyeong Jae Kim Dongun Lee Jung Yun Kang Dong Min Shin Jeong Hee Hong |
| author_facet | Eun Sun Lee Hyeong Jae Kim Dongun Lee Jung Yun Kang Dong Min Shin Jeong Hee Hong |
| author_sort | Eun Sun Lee |
| collection | DOAJ |
| description | Abstract Fibroblast-like synoviocytes (FLSs) and osteoclasts are central cells in the maintenance of joint homeostasis. Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints that induces cytokine-activated FLSs and progressive bone erosion. Interactions between FLSs and other cells, such as T cells and B cells, have been recognized in the development of RA. Here we hypothesized that calcium released from bone by mature osteoclasts might activate FLSs, which are also affected by inflammatory cytokines in the inflamed synovium. Osteoclastogenesis occurs in the presence of cytokine-stimulated FLS medium, and calcium released from the bone disc activates FLS migration. We first investigated the calcium and cytokine feedback loop between FLSs and osteoclast maturation. Moreover, by addressing the role of the sodium-bicarbonate cotransporter NBCn1 in osteoclastogenesis, we found that the inhibition of NBCn1 attenuated the infinite calcium and cytokine feedback loop between FLSs and osteoclasts. In a collagen-induced arthritis mouse model, the inhibition of NBC reduced the RA pathological phenotype and bone resorption area in the femur. These results suggest that modulation of the crosstalk between FLSs and osteoclasts by inhibiting the calcium and cytokine feedback loop could be considered to develop pioneering strategies to combat RA severity and dysregulated bone homeostasis. |
| format | Article |
| id | doaj-art-1495aaaabab74e65bf15d59c9e2c6af9 |
| institution | DOAJ |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-1495aaaabab74e65bf15d59c9e2c6af92025-08-20T03:05:57ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-02-0157240241910.1038/s12276-025-01401-8Rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loopEun Sun Lee0Hyeong Jae Kim1Dongun Lee2Jung Yun Kang3Dong Min Shin4Jeong Hee Hong5Department of Physiology, College of Medicine, Gachon University, Lee Gil Ya Cancer and Diabetes InstituteDepartment of Physiology, College of Medicine, Gachon University, Lee Gil Ya Cancer and Diabetes InstituteDepartment of Health Sciences and Technology, GAIHST, Lee Gil Ya Cancer and Diabetes InstituteDepartment of Dental Hygiene, College of Software Digital Healthcare Convergence, Yonsei UniversityDepartment of Oral Biology, Yonsei University College of DentistryDepartment of Physiology, College of Medicine, Gachon University, Lee Gil Ya Cancer and Diabetes InstituteAbstract Fibroblast-like synoviocytes (FLSs) and osteoclasts are central cells in the maintenance of joint homeostasis. Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints that induces cytokine-activated FLSs and progressive bone erosion. Interactions between FLSs and other cells, such as T cells and B cells, have been recognized in the development of RA. Here we hypothesized that calcium released from bone by mature osteoclasts might activate FLSs, which are also affected by inflammatory cytokines in the inflamed synovium. Osteoclastogenesis occurs in the presence of cytokine-stimulated FLS medium, and calcium released from the bone disc activates FLS migration. We first investigated the calcium and cytokine feedback loop between FLSs and osteoclast maturation. Moreover, by addressing the role of the sodium-bicarbonate cotransporter NBCn1 in osteoclastogenesis, we found that the inhibition of NBCn1 attenuated the infinite calcium and cytokine feedback loop between FLSs and osteoclasts. In a collagen-induced arthritis mouse model, the inhibition of NBC reduced the RA pathological phenotype and bone resorption area in the femur. These results suggest that modulation of the crosstalk between FLSs and osteoclasts by inhibiting the calcium and cytokine feedback loop could be considered to develop pioneering strategies to combat RA severity and dysregulated bone homeostasis.https://doi.org/10.1038/s12276-025-01401-8 |
| spellingShingle | Eun Sun Lee Hyeong Jae Kim Dongun Lee Jung Yun Kang Dong Min Shin Jeong Hee Hong Rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loop Experimental and Molecular Medicine |
| title | Rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loop |
| title_full | Rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loop |
| title_fullStr | Rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loop |
| title_full_unstemmed | Rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loop |
| title_short | Rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loop |
| title_sort | rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loop |
| url | https://doi.org/10.1038/s12276-025-01401-8 |
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