Enhanced BMP-2/BMP-4 ratio in patients with peripheral spondyloarthritis and in cytokine- and stretch-stimulated mouse chondrocytes.
Enhanced BMP-2/BMP-4 ratio in patients with peripheral spondyloarthritis and in cytokine- and stretch-stimulated mouse chondrocytes.
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DOI：
10.1186/s13075-020-02330-9
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发表时间：
2020-10-12
影响因子：
4.9
通讯作者：
Bougault C
中科院分区：
文献类型：
--
作者：
Briolay A;El Jamal A;Arnolfo P;Le Goff B;Blanchard F;Magne D;Bougault C
Excessive bone formation in the entheses is one of the features of peripheral spondyloarthritis (SpA). Complex pathological mechanisms connecting inflammation, mechanical stress, and ossification are probably involved. We focused on bone morphogenetic protein (BMP)-2, -4, and -7 as possible mediators of this process. BMP-2, -4, and -7 concentration was measured by ELISA in synovial fluids (SFs) of SpA (n = 56) and osteoarthritic (n = 21) patients. Mouse organotypic ankle cultures were challenged by a pro-inflammatory cocktail. Mouse primary chondrocytes, osteoblasts, or tenocytes were treated with TNF-α, interleukin (IL)-17, or IL-22 and/or subjected to cyclic stretch, or with recombinant BMP-2 or -4. In SpA SFs, if BMP-7 was barely detectable, BMP-2 concentration was higher and BMP-4 was lower than in osteoarthritic samples, so that BMP-2/BMP-4 ratio augmented 6.5 folds (p < 0.001). In SpA patients, TNF-α, IL-6, and IL-17 levels correlated this ratio (n = 21). Bmp-2/Bmp-4 ratio was similarly enhanced by cytokine treatment in explant and cell cultures, at mRNA level. In particular, simultaneous application of TNF-α and cyclical stretch induced a 30-fold increase of the Bmp-2/Bmp-4 ratio in chondrocytes (p = 0.027). Blockade of prostaglandin E2 and IL-6 production had almost no effect on the stretch-induced regulation of Bmp-2 or -4. Osteoinductive effects of BMP-4, and to a lesser extend BMP-2, were identified on cultured chondrocytes and tenocytes. Our results first settle that BMP factors are locally deregulated in the SpA joint. An unexpected decrease in BMP-4 could be associated to an increase in BMP-2, possibly in response to mechanical and/or cytokine stimulations.
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影响因子：
27.4
作者：
Benjamin, M.;Toumi, H.;McGonagle, D.
通讯作者：
McGonagle, D.
影响因子：
3.9
作者：
Chen, Hung-An;Chen, Chun-Hsiung;Chou, Chung-Tei
通讯作者：
Chou, Chung-Tei
相反的 TNF-α/IL-1β 和 BMP-2 激活的 MAPK 信号通路汇聚在 Runx2 上，调节 BMP-2 诱导的成骨细胞分化
影响因子：
9
作者：
通讯作者：
--
影响因子：
4.3
作者：
de Sousa, Eduardo Branco;dos Santos Junior, Gilson Costa;Aguiar, Diego Pinheiro
通讯作者：
Aguiar, Diego Pinheiro
影响因子：
2.8
作者：
Graham, Tisheeka R.;Odero-Marah, Valerie A.;Chung, Leland W.;Agrawal, Krishna C.;Davis, Rodney;Abdel-Mageed, Asim B.
通讯作者：
Abdel-Mageed, Asim B.