What question did this study set out to answer?

The aim of the study is to explore the anti-inflammatory effects of betulin on osteoarthritis synovial fibroblasts and the underlying mechanisms.

March 23, 2026Open Access

Betulin inhibits inflammatory factors synthesis in osteoarthritis synovial fibroblasts by suppressing the PI3K, Akt, and mTOR pathways and activating miR-5006-5p

Key Points

The aim of the study is to explore the anti-inflammatory effects of betulin on osteoarthritis synovial fibroblasts and the underlying mechanisms.
Utilized high-throughput cytokine array to measure inflammatory factors in OASFs.
Analyzed clinical tissues and GEO database for CHI3L1 and ICAM-1 levels.
Examined the effects of betulin on signaling pathways in vitro and in ACLT-induced OA rats.
Conducted molecular docking analysis to predict interactions between betulin, CHI3L1, and ICAM-1.
Betulin significantly inhibits the synthesis of CHI3L1 and ICAM-1 in OASFs.
CHI3L1 and ICAM-1 levels are elevated in OA patients compared to healthy individuals.
Mechanism involves suppression of the PI3K, Akt, and mTOR pathways and activation of miR-5006-5p.
Molecular docking suggests betulin interacts directly with CHI3L1 and ICAM-1.

Abstract

Osteoarthritis (OA) is a widespread joint condition often linked to aging and obesity, resulting in pain, joint dysfunction, and disability.Betulin, a lupane-type pentacyclic triterpene alcohol extracted from birch trees, exhibits anti-inflammatory properties; however, its anti-inflammatory effects in OA remain largely unknown.Our high-throughput cytokine array data exhibit that betulin inhibits two key inflammatory factors, CHI3L1 and ICAM-1, in OA synovial fibroblasts (OASFs).Results from the GEO database and our clinical tissues confirm that CHI3L1 and ICAM-1 levels are markedly higher in OA patients compared to healthy individuals.Furthermore, anterior cruciate ligament transection (ACLT)-induced OA rats exhibited upregulated CHI3L1 and ICAM-1 expression.Mechanistically, we demonstrated that betulin inhibits CHI3L1 and ICAM-1 synthesis in OASFs by inhibiting the PI3K, Akt, and mTOR pathways and activating miR-5006-5p.Importantly, molecular docking analysis predicted an interaction between betulin with CHI3L1 and ICAM-1, suggesting its direct effects.Our investigation suggests that betulin is a leading candidate for OA management.

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