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IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis.

Title
IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis.
Author
성일훈
Keywords
Ankylosing spondylitis; Osteoblastic activity and differentiation; IL-17A; JAK2/STAT3 signaling
Issue Date
2018-06
Publisher
BIOMED CENTRAL LTD
Citation
ARTHRITIS RESEARCH & THERAPY, v. 20, Article no. 115
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: TNF alpha, 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.
URI
https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-018-1582-3http://repository.hanyang.ac.kr/handle/20.500.11754/119154
ISSN
1478-6354; 1478-6362
DOI
10.1186/s13075-018-1582-3
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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