Sulfurous thermal waters stimulate the osteogenic differentiation of human mesenchymal stromal cells - An in vitro study

Biomed Pharmacother. 2020 Sep:129:110344. doi: 10.1016/j.biopha.2020.110344. Epub 2020 Jun 9.

Abstract

Strategies aimed at delaying the onset of bone tissue degeneration and the resulting skeletal fragility are key to decrease the risk of bone fracture correlated to ageing. The therapeutic properties of sulfurous thermal waters (STWs), rich in hydrogen sulfide (H2S), have been claimed for centuries. However, the direct regulation of bone cells by STWs has not been investigated yet. Here we aimed at analyzing the effect of STWs on cultured human mesenchymal stromal cells (hMSCs) derived from bone tissue. Two concentrations of STWs from 2 health spa centers in Italy (here named STW-1 and STW-2) containing, respectively, high and moderate quantities of H2S, were added to the culture media. Cytotoxicity and osteogenic differentiation were evaluated. We provided first evidence that treatment of hMSCs with STWs results in a sharp increase in intracellular H2S content, coherent with the different concentrations of H2S, thereby reveling that STWs-released H2S is internalized by cells. STWs treatment significantly induced osteogenic differentiation of hMSCs. In particular, mineral apposition was increased with a similar pattern by the two STWs, while mRNA expression of osteogenic markers (BSP, OC, RUNX-2, OPN) was differently affected. Only STW-2 induced a significant, dose-dependent increase in these gene expression. These findings support the rationale for the use of STWs as a complementary treatment of bone wasting diseases.

Keywords: Complementary medicine; Hydrogen sulfide; Mesenchymal stromal cells; Mineralization; Osteogenesis; Sulfurous thermal water.

MeSH terms

  • Aged
  • Balneology*
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Hydrogen Sulfide / metabolism
  • Hydrogen Sulfide / pharmacology*
  • Integrin-Binding Sialoprotein / genetics
  • Integrin-Binding Sialoprotein / metabolism
  • Italy
  • Male
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Middle Aged
  • Mineral Waters*
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteogenesis / drug effects*
  • Osteopontin / genetics
  • Osteopontin / metabolism

Substances

  • BGLAP protein, human
  • Core Binding Factor Alpha 1 Subunit
  • IBSP protein, human
  • Integrin-Binding Sialoprotein
  • Mineral Waters
  • RUNX2 protein, human
  • SPP1 protein, human
  • Osteocalcin
  • Osteopontin
  • Hydrogen Sulfide