KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK

Laura Salvadori, Maria Laura Belladonna, Beatrice Castiglioni, Martina Paiella, Eleonora Panfili, Tommaso Manenti, Catia Ercolani, Luca Cornioli, Sara Chiappalupi, Giulia Gentili, Massimiliano Leigheb, Guglielmo Sorci, Michela BOSETTI, Nicoletta FILIGHEDDU, Francesca Riuzzi

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

The imbalance in osteoblast (OB)-dependent bone formation in favor of osteoclast (OC)-dependent bone resorption is the main cause of loss of tissue mineral mass during bone remodeling leading to osteoporosis conditions. Thus, the suppression of OC activity together with the improvement in the OB activity has been proposed as an effective therapy for maintaining bone mass during aging. We tested the new dietary product, KYMASIN UP containing standardized Withania somnifera, Silybum marianum and Trigonella foenum-graecum herbal extracts or the single extracts in in vitro models mimicking osteoclastogenesis (i.e., RAW 264.7 cells treated with RANKL, receptor activator of nuclear factor kappa-Beta ligand) and OB differentiation (i.e., C2C12 myoblasts treated with BMP2, bone morphogenetic protein 2). We found that the dietary product reduces RANKL-dependent TRAP (tartrate-resistant acid phosphatase)-positive cells (i.e., OCs) formation and TRAP activity, and down-regulates osteoclastogenic markers by reducing Src (non-receptor tyrosine kinase) and p38 MAPK (mitogen-activated protein kinase) activation. Withania somnifera appears as the main extract responsible for the anti-osteoclastogenic effect of the product. Moreover, KYMASIN UP maintains a physiological release of the soluble decoy receptor for RANKL, OPG (osteoprotegerin), in osteoporotic conditions and increases calcium mineralization in C2C12-derived OBs. Interestingly, KYMASIN UP induces differentiation in human primary OB-like cells derived from osteoporotic subjects. Based on our results, KYMASIN UP or Withania somnifera-based dietary supplements might be suggested to reverse the age-related functional decline of bone tissue by re-balancing the activity of OBs and OCs, thus improving the quality of life in the elderly and reducing social and health-care costs.
Lingua originaleInglese
pagine (da-a)3053
RivistaNutrients
Volume14
Numero di pubblicazione15
DOI
Stato di pubblicazionePubblicato - 2022

Keywords

  • Animals
  • Biological Products
  • Bone Resorption
  • Cell Differentiation
  • Dietary Supplements
  • Humans
  • Mice
  • Osteoblasts
  • Osteoclasts
  • Osteogenesis
  • RANK Ligand
  • RANKL
  • RAW 264.7 Cells
  • age-related diseases
  • natural product
  • osteoblast
  • osteoclast
  • p38 Mitogen-Activated Protein Kinases
  • signaling pathways

Fingerprint

Entra nei temi di ricerca di 'KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK'. Insieme formano una fingerprint unica.

Cita questo