AI Article Synopsis

  • * Treatment with hyaluronidase (HA'ase) or knocking down hyaluronan synthase 2 (HAS2) increased RANKL expression, while the presence of high molecular weight HA or TGF-β1 decreased RANKL levels in similar conditions.
  • * The study suggests that HA accumulation in bone marrow cells can modulate osteoclast activity by affecting RANKL expression through the Vitamin D receptor (VDR) and STAT3 signaling pathways.

Article Abstract

Hyaluronic acid (HA) has a pivotal role in bone and cartilage metabolism. In this study, we investigated the effect and underlying mechanisms of HA accumulation on the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) induced by 1α,25(OH)D and dexamethasone in stromal cells, which support osteoclastogenesis. Degradation of HA by hyaluronidase (HA'ase) treatment enhanced the expression of RANKL in ST2 cells stimulated with 1α,25(OH)D and dexamethasone. Down-regulation of hyaluronan synthase 2 (HAS2) expression by siRNA also stimulated RANKL expression induced by 1α,25(OH)D and dexamethasone. Results from a cell co-culture system with bone marrow cell showed that 1α,25(OH)D and dexamethasone-induced RANKL expression in HA'ase treated- and HAS2 siRNA transfected-ST2 cells was down-regulated by treatment of cells with high molecular weight HA. In contrast, transforming growth factor-β1 (TGF-β1), which stimulates HAS2 expression and HA synthesis, down-regulated RANKL expression induced by 1α,25(OH)D and dexamethasone. Interestingly, knockdown of has2 gene enhanced the expression of vitamin D receptor (VDR) and phosphorylation of signal transducers and activator of transcription 3 (STAT3) in ST2 cells stimulated by 1α,25(OH)D and dexamethasone. These results indicate that accumulation of HA in bone marrow cells may affect RANKL-mediated osteoclast-supporting activity via regulation of VDR and STAT3 signaling pathways.

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Source
http://dx.doi.org/10.1016/j.bbrc.2019.03.137DOI Listing

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