Bone morphogenetic proteins and Dickkopf-1 in ankylosing spondylitis

Liao, Hsien Tzung; Lin, Yuh Feng; Tsai, Chang Youh; Chou, Teh-Ying

doi:10.1080/03009742.2017.1287305

Cited by 33 publications

(27 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DKK1 is an inhibitor of the Wnt/β-catenin pathway and a vital mediator in the progression of AS 29, 30, 31. A lower level of DKK1 leads to fusion of the sacroiliac joints by increasing WNT protein-associated osteoblast activity and new bone formation 32 , 33 . VEGF, a signal protein that plays a crucial role in angiogenesis, participates in endochondral ossification 34 .…”

Section: Discussionmentioning

confidence: 99%

miR-17-5p Regulates Heterotopic Ossification by Targeting ANKH in Ankylosing Spondylitis

Xiong

Zhu

Jiang

et al. 2019

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized with heterotopic ossification of the axis joints ligaments, resulting in joint disability. MicroRNAs (miRNAs) are regulators of mRNAs that play a crucial role in the AS pathological process. Here, we showed that the level of miR-17-5p was significantly higher in fibroblasts and ligament tissues from AS patients as compared to the non-AS individuals. Knockdown of the miR-17-5p from the fibroblasts derived from AS patients exhibited decreased osteogenic differentiation and ossification. On the other hand, AS patient-derived fibroblasts overexpressing miR-17-5p displayed the increased osteogenesis. Furthermore, inhibition of miR-17-5p ameliorated osteophyte formation, and the sacroiliitis phenotype in AS rats received emulsified collagen. Mechanistically, miR-17-5p regulated osteogenic differentiation by targeting the 3ʹ UTR of ankylosis protein homolog (ANKH). Also, downregulation of miR-17-5p slowed AS progression through regulation of cytokines, such as dickkopf-1 (DKK1) and vascular endothelial growth factor (VEGF). In conclusion, our findings reveal a role of the miR-17-5p-ANKH axis in the regulation of heterotopic ossification, which is essential for therapeutic intervention in heterotopic ossification in AS.

show abstract

Section: Discussionmentioning

confidence: 99%

miR-17-5p Regulates Heterotopic Ossification by Targeting ANKH in Ankylosing Spondylitis

Xiong

Zhu

Jiang

et al. 2019

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

show abstract

“… 112 Serum BMP-7 levels and the BMP-7/DKK-1 ratio have been reported to correlate significantly with sacroiliitis severity, ‘osteoproliferation-weighted’ radiographic indices and disease duration in AS. 113 The authors also found a significant correlation between BMP-2, BMP-4 and BMP-6 and BASRI-total and disease duration. Thus, there are both genetic and correlative serum data for a role of BMPs in the formation of bone in AS.…”

Section: Mechanisms Of Bone Pathophysiology In Spamentioning

confidence: 87%

Loss and gain of bone in spondyloarthritis: what drives these opposing clinical features?

Clunie

Horwood

2020

Therapeutic Advances in Musculoskeletal

View full text Add to dashboard Cite

The breadth of bone lesion types seen in spondyloarthritis is unprecedented in medicine and includes increased bone turnover, bone loss and fragility, osteitis, osteolysis and erosion, osteosclerosis, osteoproliferation of soft tissues adjacent to bone and spinal skeletal structure weakness. Remarkably, these effects can be present simultaneously in the same patient. The search for a potential unifying cause of effects on the skeleton necessarily focuses on inflammation arising from the dysregulation of immune response to microorganisms, particularly dysregulation of TH17 lymphocytes, and the dysbiosis of established gut and other microbiota. The compelling notion that a common antecedent pathological mechanism affects existing bone and tissues with bone-forming potential (entheses), simultaneously with variable effect in the former but bone-forming in the latter, drives basic research forward and focuses our awareness on the effects on these bone mechanisms of the increasing portfolio of targeted immunotherapies used in the clinic.

show abstract

“…The consistency of our results was validated with respect to previous studies that assessed BMP contents in SF from OA patients [ 31 – 34 ]. Three independent studies have demonstrated that BMP-2 serum concentration was in the range of 100 pg/mL and neatly higher in ankylosing spondylitis patients than in healthy controls [ 14 , 15 , 35 ]. Our result showing that BMP-2 content is particularly elevated in SpA SF seems thus coherent, especially because a correlation between serum and SF BMP-2 levels was expected [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the drop of BMP-4 levels in SpA SF was a particularly striking result. Indeed, BMP-4 serum content has been shown to be either equal or superior in SpA patients than in healthy donors [ 14 , 15 , 35 ]. However, a decrease in BMP-4 expression has already been observed in synovial tissue of patients with OA and rheumatoid arthritis [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Enhanced BMP-2/BMP-4 ratio in patients with peripheral spondyloarthritis and in cytokine- and stretch-stimulated mouse chondrocytes

et al. 2020

View full text Add to dashboard Cite

Background 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. Methods 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. Results 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. Conclusions 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.

show abstract

Bone morphogenetic proteins and Dickkopf-1 in ankylosing spondylitis

Cited by 33 publications

References 39 publications

miR-17-5p Regulates Heterotopic Ossification by Targeting ANKH in Ankylosing Spondylitis

miR-17-5p Regulates Heterotopic Ossification by Targeting ANKH in Ankylosing Spondylitis

Loss and gain of bone in spondyloarthritis: what drives these opposing clinical features?

Enhanced BMP-2/BMP-4 ratio in patients with peripheral spondyloarthritis and in cytokine- and stretch-stimulated mouse chondrocytes

Contact Info

Product

Resources

About