Background Autophagy induction is an effective approach for OA therapy. IL-1β is one of the major inflammatory cytokines linked to OA pathological progression, and its receptor blockade interrupts OA cartilage destruction. The objective of this study was to decipher the link between autophagy and regulatory mechanism of IL-1β and to investigate the effect of IL-1β receptor blockade by IL-1 receptor antagonist (IL-1Ra) combined with or without an autophagy inducer (TAT-Beclin1) on extracellular matrix (ECM) in OA chondrocytes in vitro and in vivo. Methods IL-1β-treated rat and human OA chondrocytes were cultured in response to IL-1Ra. The expression and distribution of signal molecules regulating ECM synthesis and autophagy were investigated via western blotting, immunoprecipitation, real-time PCR, immunofluorescence, and transmission electron microscope technique. Furthermore, after intra-articular injection of IL-1Ra, TAT-Beclin1, and a combination of both in a rat OA model established by anterior cruciate ligament transection and medial meniscus resection, the morphological changes of cartilage and related signal molecule expression levels were monitored using H.E., Safranin O-Fast green, and immunohistochemistry staining. Results Reduced autophagy by IL-1β contributed to ECM degradation, and blockade of IL-1β by IL-1Ra restored autophagy and attenuated ECM degradation in rat and human OA chondrocytes, as well as in a rat OA model. Akt/mTOR/ULK1, Akt/mTOR/NF-κB, and LC3B deacetylation were involved in autophagy regulated by IL-1β. Intra-articular injection of IL-1Ra combined with TAT-Beclin1 was more effective than IL-1Ra alone. Conclusions IL-1Ra restored autophagy and attenuated ECM degradation, with an implication that blocking IL-1β combined with enhancing autophagy might be a potential therapeutic strategy for OA. Electronic supplementary material The online version of this article (10.1186/s13075-019-1952-5) contains supplementary material, which is available to authorized users.

Despite various animal serums being used widely to culture chondrocytes, the regulatory mechanism of serum on chondrocyte activities has not been elucidated. In the present study, human osteoarthritis (OA) chondrocytes were used to perform in vitro investigations on the effect of different concentrations of bovine fetal serum on extracellular matrix synthesis, cell proliferation and autophagy using the Cell Counting Kit‑8 analysis, a laser‑scanning confocal microscope, and western blot analysis. The results demonstrated that 5% serum exerted a chondroprotective effect more than the other concentrations of serum, as it simultaneously promoted cell proliferation, autophagy, and ECM synthesis in human OA chondrocytes. Furthermore, the decreased mechanistic target of rapamycin (mTOR) and increased Akt were observed in 5% serum‑treated OA chondrocytes. Either mTOR or Akt inhibitor influenced the effect of 5% serum on cell proliferation and autophagy in human OA chondrocytes, which was associated with LC‑3B or B‑cell lymphoma-2 (Bcl‑2) signal molecules. Consistent with previous studies, the present study proposes that 5% serum promotes cell proliferation via the Akt/Bcl‑2 axis and induces autophagy via the mTOR/LC‑3B axis in human OA chondrocytes. Furthermore, the different roles of Akt and mTOR in the cell processes of human OA chondrocytes require consideration for preclinical and clinical therapy of OA.