Promotion of osteogenesis by Sweroside via BMP2-involved signaling in postmenopausal osteoporosis

Phytother Res. 2021 Dec;35(12):7050-7063. doi: 10.1002/ptr.7336. Epub 2021 Nov 24.

Abstract

Phlomis umbrosa has been traditionally used for bone diseases in traditional Korean Medicine. Sweroside (SOS), marker compounds of P. umbrosa, has been known to promote osteoblast differentiation. In this study, ameliorative effects of SOS on osteoporosis and potential target pathway were investigated. Ovariectomized mice were administered three doses of SOS three times a week for 4 weeks after inducing osteoporosis. Bone mineral content (BMC) and bone mineral density (BMD) were analyzed by dual energy X-ray absorptiometry. A human osteosarcoma cell line (SaOS-2) was differentiated to clarify the promoting effects of SOS on osteoblast differentiation and bone formation. Osteoblastic bone-forming markers were evaluated in lumbar vertebrae (LV) and mineralized SaOS-2 cells. SOS markedly elevated BMC and BMD levels and attenuated the bone marrow adipocytes in the femoral shaft. SOS increased the formation of bone matrix in SaOS-2 cells. Bone morphogenetic protein-2 (BMP2) and runt-related transcription factor 2 (CBFA1) in LV and SaOS-2 cells were up-regulated by SOS. SOS increased alkaline phosphatase (ALPL), osteopontin (SPP1), and bone sialoprotein-1 (BSPH1). In conclusion, SOS induced the formation of mineralized bone matrix by regulating BMP2/CBFA1-mediated molecules. Therefore, SOS could be a therapeutic compound of treatment for osteoporosis by producing the new bone matrix.

Keywords: Sweroside; bone formation; osteoblasts; postmenopausal osteoporosis.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2*
  • Cell Differentiation
  • Disease Models, Animal
  • Female
  • Humans
  • Iridoid Glucosides / pharmacology*
  • Mice
  • Osteoblasts
  • Osteogenesis
  • Osteoporosis / drug therapy*
  • Osteoporosis, Postmenopausal
  • Seminal Vesicle Secretory Proteins*
  • Signal Transduction

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bsph1 protein, mouse
  • Iridoid Glucosides
  • Seminal Vesicle Secretory Proteins
  • sweroside