IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis.
IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis.
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DOI：
10.1186/s13075-018-1582-3
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发表时间：
2018-06-07
影响因子：
4.9
通讯作者：
Kim TH
中科院分区：
文献类型：
--
作者：
Jo S;Wang SE;Lee YL;Kang S;Lee B;Han J;Sung IH;Park YS;Bae SC;Kim TH
IL-17A最近被认为是调节强直性脊柱炎（as）中广泛炎症和异常骨形成的潜在靶点。阻断IL-17A有望抑制骨性强直。在此，我们研究了抗IL-17A药物在AS中的作用。采用ELISA法测定强直性脊柱炎（AS）、类风湿关节炎（RA）、骨关节炎（OA）和健康对照（HC）患者血清和滑液中TNFα、IL-17A和il -12/ 23p40水平。手术时从10例AS患者和10例非炎性脊柱疾病对照（Ct）患者的小关节突关节处获取骨组织样本。在体外用原代骨源性细胞（BdCs）和AS患者血清评估IL-17A、生物阻断剂、Janus激酶2 （JAK2）和非受体酪氨酸激酶的功能相关性。AS患者体液中IL-17A和il -12/ 23p40的基础水平升高。JAK2在AS患者的骨组织和原发BdCs中也高表达。此外，在原代ct - bdc中添加外源性IL-17A可促进成骨刺激诱导的ALP活性和矿化的增加。有趣的是，用AS患者的血清阻断IL-17A，通过抑制JAK2磷酸化和下调成骨细胞相关基因，减弱了Ct和AS- bdc中ALP活性和矿化。此外，JAK2抑制剂有效地降低了JAK2驱动的ALP活性和JAK2介导的事件。我们的研究结果表明，IL-17A通过JAK2/STAT3信号调节成骨细胞的活性和分化。它们阐明了AS的发病机制，并为临床AS强直提供了新的合理治疗方法。本文的在线版本（10.1186/s13075-018-1582-3）包含补充材料，仅供授权用户使用。
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. 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. 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. 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. The online version of this article (10.1186/s13075-018-1582-3) contains supplementary material, which is available to authorized users.
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影响因子：
--
作者：
Barkham, Nick;Keen, Helen I.;Emery, Paul
通讯作者：
Emery, Paul
DOI：
10.1073/pnas.1208916109
发表时间：
2012-08-28
影响因子：
11.1
作者：
Boonrungsiman, Suwimon;Gentleman, Eileen;Stevens, Molly M.
通讯作者：
Stevens, Molly M.
影响因子：
--
作者：
Haroon, Nigil;Inman, Robert D.;Learch, Thomas J.;Weisman, Michael H.;Lee, MinJae;Rahbar, Mohammad H.;Ward, Michael M.;Reveille, John D.;Gensler, Lianne S.
通讯作者：
Gensler, Lianne S.
影响因子：
27.4
作者：
van der Heijde D;Deodhar A;Wei JC;Drescher E;Fleishaker D;Hendrikx T;Li D;Menon S;Kanik KS
通讯作者：
Kanik KS
影响因子：
27.4
作者：
Molnar C;Scherer A;Baraliakos X;de Hooge M;Micheroli R;Exer P;Kissling RO;Tamborrini G;Wildi LM;Nissen MJ;Zufferey P;Bernhard J;Weber U;Landewé RBM;van der Heijde D;Ciurea A;Rheumatologists of the Swiss Clinical Quality Management Program
通讯作者：
Rheumatologists of the Swiss Clinical Quality Management Program