Effect of hyaluronic acid on paracrine signaling of osteoblasts from mesenchymal stromal cells: potential impact on bone regeneration

Clin Oral Investig. 2021 Jul;25(7):4571-4578. doi: 10.1007/s00784-020-03771-x. Epub 2021 Jan 7.

Abstract

Objectives: This study evaluated hyaluronic acids (HA) with different molecular weights as potential matrices for tissue-engineered bone grafting and their possible influence on the paracrine mechanisms of adipose-derived mesenchymal stromal cells.

Material and methods: Murine adipose mesenchymal stromal cells (mASCs) on the fourth passage were seeded in 96-well plates, osteoinduced for 27 days and exposed for 3 days to low (HA-LW) and high/low molecular weight (HA-HLW) at previously defined concentrations. Cytokines IGF-1, VEGF, FGF-2, and BMP-2 were evaluated by quantification in the supernatant.

Results: Greater expression of growth factors was observed in groups with HA-HLW compared to HA-LW. Results indicated that differentiated cells secreted fewer cytokines, namely VEGF, FGF, and BMP-2 than undifferentiated mASCs (p < 0.05). IGF-1 showed its greatest expression in the mASC HA-LW group (p < 0.05).

Conclusions: The application of HA-HLW as cell matrix in tissue engineering did not compromise mASC paracrine effect. Also, the association of HA-HLW matrix and mASCs resulted in greater expression of osteogenic growth factors. Longer periods of cell differentiation seemed to negatively affect their capacity for local paracrine stimulation.

Clinical relevance: The use of HA-HLW as matrix for undifferentiated ASCs can be positive for bone regeneration, favoring its application as cell matrix in bone grafting procedures.

Keywords: Bone regeneration; Cytokine; Mesenchymal stem cell; Paracrine.

MeSH terms

  • Adipose Tissue
  • Animals
  • Bone Regeneration
  • Cell Differentiation
  • Cells, Cultured
  • Hyaluronic Acid
  • Mesenchymal Stem Cells*
  • Mice
  • Osteoblasts
  • Osteogenesis
  • Paracrine Communication

Substances

  • Hyaluronic Acid