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Background <p>Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by pathological bone formation. Synovial fibroblasts are key effector cells in this process, and their dysregulated osteogenic transformation is a critical event. The role of microRNA‑21 (miR‑21) and the mitogen-activated protein kinase (MAPK)/nuclear factor kappa-B‌ (NF‑κB) pathway in inflammation and bone metabolism is established; however, whether miR‑21 promotes AS fibroblast osteogenesis specifically via this pathway is unclear. This study aimed to determine whether miR-21 promotes osteogenic transformation and bone metabolism in AS synovial fibroblasts via the MAPK/NF‑κB pathway.</p> Methods <p>Gain‑ and loss‑of‑function of miR‑21 was achieved in AS synovial fibroblasts by transfection with miR‑21 mimic or inhibitor, followed by evaluation of proliferation, osteogenic differentiation (alkaline phosphatase/alizarin red staining), and MAPK/NF‑κB pathway activity. In a proteoglycan‑induced arthritis (PGIA) mouse model, miR‑21 was inhibited by Antagomir to assess spinal pathology, serum inflammatory cytokines, bone metabolism markers, and MAPK/NF‑κB signaling.</p> Results <p>In vitro, miR-21 overexpression significantly promoted fibroblast proliferation, osteogenic differentiation, and activated the MAPK/NF-κB pathway, while its inhibition had opposite effects. In vivo, AntagomiR-21 treatment ameliorated spinal cartilage damage, reduced serum levels of inflammatory cytokines (IL-6, IL-1β, TNF-α) and bone metabolism markers (RANKL/OPG), and suppressed the MAPK/NF-κB pathway in PGIA mice.</p> Conclusions <p>Our findings suggest that miR-21 is associated with synovial fibroblast proliferation and osteogenesis, potentially via the MAPK/NF‑κB pathway, and that its inhibition alleviates inflammatory arthritis phenotypes in mice. These observations indicate that miR‑21 may warrant further investigation as a candidate target in AS-related inflammation and cartilage pathology.</p>

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MiR-21 promotes osteogenic transformation in ankylosing spondylitis fibroblasts and modulates bone metabolism in a murine arthritis model potentially involving the MAPK NF-κB pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • Weiwei Pan,
  • Wenbiao Zheng,
  • Weiqian Wu,
  • Fanghu Chen

摘要

Background

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by pathological bone formation. Synovial fibroblasts are key effector cells in this process, and their dysregulated osteogenic transformation is a critical event. The role of microRNA‑21 (miR‑21) and the mitogen-activated protein kinase (MAPK)/nuclear factor kappa-B‌ (NF‑κB) pathway in inflammation and bone metabolism is established; however, whether miR‑21 promotes AS fibroblast osteogenesis specifically via this pathway is unclear. This study aimed to determine whether miR-21 promotes osteogenic transformation and bone metabolism in AS synovial fibroblasts via the MAPK/NF‑κB pathway.

Methods

Gain‑ and loss‑of‑function of miR‑21 was achieved in AS synovial fibroblasts by transfection with miR‑21 mimic or inhibitor, followed by evaluation of proliferation, osteogenic differentiation (alkaline phosphatase/alizarin red staining), and MAPK/NF‑κB pathway activity. In a proteoglycan‑induced arthritis (PGIA) mouse model, miR‑21 was inhibited by Antagomir to assess spinal pathology, serum inflammatory cytokines, bone metabolism markers, and MAPK/NF‑κB signaling.

Results

In vitro, miR-21 overexpression significantly promoted fibroblast proliferation, osteogenic differentiation, and activated the MAPK/NF-κB pathway, while its inhibition had opposite effects. In vivo, AntagomiR-21 treatment ameliorated spinal cartilage damage, reduced serum levels of inflammatory cytokines (IL-6, IL-1β, TNF-α) and bone metabolism markers (RANKL/OPG), and suppressed the MAPK/NF-κB pathway in PGIA mice.

Conclusions

Our findings suggest that miR-21 is associated with synovial fibroblast proliferation and osteogenesis, potentially via the MAPK/NF‑κB pathway, and that its inhibition alleviates inflammatory arthritis phenotypes in mice. These observations indicate that miR‑21 may warrant further investigation as a candidate target in AS-related inflammation and cartilage pathology.