RUNX2 promotes the suppression of osteoblast function and enhancement of osteoclast activity by multiple myeloma cells

Med Oncol. 2023 Mar 10;40(4):115. doi: 10.1007/s12032-023-01960-8.

Abstract

RUNX2 is a transcription factor that participates in osteoblast differentiation and chondrocyte maturation and plays an important role in the invasion and metastasis of cancers. With the deepening of research, evidence has indicated the correlation between RUNX2 and bone destruction in cancers. However, the mechanisms underlying its role in multiple myeloma remain unclear. By observing the induction effects of conditioned medium from myeloma cells on preosteoblasts (MC3T3-E1) and preosteoclasts (RAW264.7) and constructing myeloma-bearing mice, we found that RUNX2 promotes bone destruction in multiple myeloma. In vitro, conditioned medium from RUNX2-overexpressing myeloma cells reduced osteoblast activity and increased osteoclast activity. In vivo, RUNX2 expression was positively correlated with bone loss in myeloma-bearing mice. These results suggest that therapeutic inhibition of RUNX2 may protect against bone destruction by maintaining the balance between osteoblast and osteoclast activity in multiple myeloma.

Keywords: Bone destruction; Multiple myeloma; Osteoblast; Osteoclast; RUNX2.

MeSH terms

  • Animals
  • Cell Differentiation
  • Core Binding Factor Alpha 1 Subunit* / metabolism
  • Core Binding Factor Alpha 1 Subunit* / pharmacology
  • Culture Media, Conditioned / metabolism
  • Humans
  • Mice
  • Multiple Myeloma* / metabolism
  • Osteoblasts / metabolism
  • Osteoclasts*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Culture Media, Conditioned
  • Runx2 protein, mouse
  • RUNX2 protein, human