Methylsulfonylmethane and mobilee prevent negative effect of IL-1β in human chondrocyte cultures via NF-κB signaling pathway

Int Immunopharmacol. 2018 Dec;65:129-139. doi: 10.1016/j.intimp.2018.10.004. Epub 2018 Oct 10.

Abstract

Nutraceuticals are compounds that serve as nutrition with an easy accessibility and favourable safety profile. Recent studies showed their potential activity on osteoarthritis (OA) inflammation and cartilage metabolism. We investigated the effect of methylsulfonylmethane (MSM) and mobilee in human OA chondrocyte cultures exposed to interleukin (IL)-1β. OA cartilage was obtained from femoral heads of five patients undergoing total replacement surgery. Chondrocytes were incubated with mobilee (200 and 500 μM) and MSM (2000 and 6000 μM) in presence of IL-1β (10 ng/mL) and nuclear factor (NF)-κB inhibitor (BAY 11-7082, 1 μM), for 24 and 48 h. Viability and apoptosis were performed by MMT and flow cytometry. The metalloproteinase (MMP)-1,-3,-13 and type II collagen (Col2a1) were analyzed by qRT-PCR and ELISA, and NF-κB activation by immunofluorescence. IL-1β stimulus determined a significant regulation of survival, apoptotic ratio, as well as of gene expression and serum levels of MMP-1,-3,-13 and Col2a1 in OA chondrocytes compared to baseline. Mobilee and MSM incubation significantly reversed the effect of IL-1β. IL-1β significantly induced NF-κB p50 nuclear translocation, which was significantly counteracted by the pre-treatment of OA chodrocytes with the tested compounds. BAY11-7082 significantly modulated MMPs and Col2a1 expression respectively to basal state. Co-treatment of IL-1β with mobilee, MSM and BAY11-7082 didn't cause changes of MMPs or Col2a1 beyond that caused by each single treatment. We demonstrated that MSM and mobilee have a beneficial effect on OA chondrocytes metabolism, probably due to the modulation of NF-κB pathway, providing a powerful rationale for the use of these substances in OA treatment.

Keywords: Chondrocyte; Methylsulfonylmethane; Mobilee; NF-κB; Osteoarthritis.

MeSH terms

  • Aged
  • Cell Survival
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Dimethyl Sulfoxide / pharmacology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Hyaluronic Acid / pharmacology*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Matrix Metalloproteinases / metabolism
  • Middle Aged
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Osteoarthritis / metabolism
  • Signal Transduction / drug effects
  • Sulfones / pharmacology*

Substances

  • Interleukin-1beta
  • NF-kappa B
  • Sulfones
  • Hyaluronic Acid
  • dimethyl sulfone
  • Matrix Metalloproteinases
  • Dimethyl Sulfoxide