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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Jo, Sungsin Wang, Sung Eun Lee, Young Lim Kang, Suman Lee, Bitnara Han, Jinil Sung, Il-Hoon Park, Ye-Soo Bae, Sang-Cheol Kim, Tae-Hwan |
| Abstract | Background IL-17A has recently emerged as a potential target that regulates the extensive inflammation and abnormal bone formation observed in ankylosing spondylitis (AS). Blocking IL-17A is expected to inhibit bony ankylosis. Here, we investigated the effects of anti IL-17A agents in AS. Methods TNFα, IL-17A, and IL-12/23 p40 levels in serum and synovial fluid from patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), osteoarthritis (OA), or healthy controls (HC) were measured by ELISA. Bone tissue samples were obtained at surgery from the facet joints of ten patients with AS and ten control (Ct) patients with noninflammatory spinal disease. The functional relevance of IL-17A, biological blockades, Janus kinase 2 (JAK2), and non-receptor tyrosine kinase was assessed in vitro with primary bone-derived cells (BdCs) and serum from patients with AS. Results Basal levels of IL-17A and IL-12/23 p40 in body fluids were elevated in patients with AS. JAK2 was also highly expressed in bone tissue and primary BdCs from patients with AS. Furthermore, addition of exogenous IL-17A to primary Ct-BdCs promoted the osteogenic stimulus-induced increase in ALP activity and mineralization. Intriguingly, blocking IL-17A with serum from patients with AS attenuated ALP activity and mineralization in both Ct and AS-BdCs by inhibiting JAK2 phosphorylation and downregulating osteoblast-involved genes. Moreover, JAK2 inhibitors effectively reduced JAK2-driven ALP activity and JAK2-mediated events. Conclusions Our findings indicate that IL-17A regulates osteoblast activity and differentiation via JAK2/STAT3 signaling. They shed light on AS pathogenesis and suggest new rational therapies for clinical AS ankylosis. |
| Related Links | https://arthritis-research.biomedcentral.com/counter/pdf/10.1186/s13075-018-1582-3.pdf |
| Ending Page | 10 |
| Page Count | 10 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14786362 |
| DOI | 10.1186/s13075-018-1582-3 |
| Journal | Arthritis Research & Therapy |
| Issue Number | 1 |
| Volume Number | 20 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2018-06-07 |
| Access Restriction | Open |
| Subject Keyword | Rheumatology Orthopedics Ankylosing spondylitis Osteoblastic activity and differentiation IL-17A JAK2/STAT3 signaling |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology Rheumatology |
| Journal Impact Factor | 4.4/2023 |
| 5-Year Journal Impact Factor | 4.9/2023 |
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