miR-214 stimulated by IL-17A regulates bone loss in patients with ankylosing spondylitis

Abstract

Objective Bone loss is common in AS, and miR-214 plays an important role in regulating bone formation. The aim of this study was to investigate the effect of miR-214, the production of which is stimulated by IL-17A, on bone loss in AS. Methods Peripheral blood was obtained from 32 patients with AS and 24 healthy controls. Levels of IL-17A, soluble RANK ligand (RANKL) and osteoprotegerin in serum were evaluated by ELISA, and the relative level of miR-214 in serum was detected by real-time quantitative PCR. In addition, we assessed the relationship between levels of miR-214, IL-17A and bone loss in primary murine osteoblasts and mouse bone marrow cells. Results The expression of RANKL and miR-214 in osteoblasts was increased following stimulation by IL-17A, and osteoblasts stimulated by IL-17A promoted the expression of miR-214 in osteoclasts and the activity of osteoclasts. We showed that osteoblast-derived miR-214 could be transferred to osteoclasts and could then regulate their activity. The levels of IL-17A and miR-214 were much higher in the serum of patients with AS than in that of healthy controls, and the relative level of miR-214 was positively correlated with the level of IL-17A in the serum and synovial fluid of the patients with AS, not healthy controls. The level of miR-214 in the serum of AS patients has potential diagnostic value. Conclusion The production of miR-214 in osteoblasts is stimulated by IL-17A. It is an important inhibitor of bone formation in AS, and the serum level of miR-214 might be of potential diagnostic value for AS.

The Potential Role of Genetics, Environmental Factors, and Gut Dysbiosis in the Aberrant Non-Coding RNA Expression to Mediate Inflammation and Osteoclastogenic/Osteogenic Differentiation in Ankylosing Spondylitis

“…Investigations have unraveled that IL-17 can activate osteoclasts (OCs) to express RANK ligand (RANKL), which then reciprocally stimulates OCs themselves by RNAK-RANKL interaction and induces bone absorption ( Page and Miossec, 2005 ; Miossec, 2009 ). IL-17A-stimulated miR214 expression in OCs is an important inhibitor for bone formation in AS patients ( Wang et al, 2013 ; Zhao et al, 2015 ; Liu et al, 2020 ). Nevertheless, adding of exogenous IL-17A into cultured normal primary bone-derived cells (BdCs) promotes OC activity and differentiation as evidenced by increased alkaline phosphatase (ALP) activity through JAK2/STAT3 pathway ( Jo et al, 2018a ; Wang et al, 2018 ).…”

MicroRNAs in Axial Spondylarthritis: an Overview of the Recent Progresses in the Field with a Focus on Ankylosing Spondylitis and Psoriatic Arthritis

“…Further, the mRNA and protein expression levels of miR-214 were positively correlated with IL-17A levels both in blood and synovial fluid of patients with AS. These results suggest an inhibitory role in bone formation for miR-214 and recommend its potential diagnostic value [ 58 ].…”

Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation

“…It has recently been reported that microRNA mir-214 mediates the capacity of IL-17A to inhibit primary murine calvaria osteoblast differentiation in vitro [ 150 ]. MiR-214 inhibits osteogenesis in vivo and in vitro [ 151 ], and IL-17A increases osteoblast miR-214 production and RANKL expression, promoting osteoclast differentiation in coculture conditions due to the reduction of the OPG/RANKL ratio.…”

“…Furthermore, knockout miR-214 in osteoblasts decreased in vivo osteoclastogenesis. Interestingly, AS patients who manifest bone loss have elevated IL-17A and miR-214 Levels in the serum and synovial fluid, indicating their potential diagnostic value in AS[ 150 ].…”