Department of Hematopathology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58, Zhongshan 2Nd Road, Guangzhou, 510080, China.
Department of Pharmacology, School of Medicine, Molecular Cancer Research Center, Sun Yat-Sen University, No.66, Gongchang Road, Shenzhen, 518107, China.
Med Oncol. 2023 Mar 10;40(4):115. doi: 10.1007/s12032-023-01960-8.
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.
RUNX2 是一种转录因子，参与成骨细胞分化和软骨细胞成熟，在癌症的侵袭和转移中发挥重要作用。随着研究的深入，有证据表明 RUNX2 与癌症中的骨破坏有关。然而，其在多发性骨髓瘤中的作用机制尚不清楚。通过观察骨髓瘤细胞条件培养基对前成骨细胞（MC3T3-E1）和前破骨细胞（RAW264.7）的诱导作用，并构建骨髓瘤荷瘤小鼠，我们发现 RUNX2 促进多发性骨髓瘤中的骨破坏。在体外，过表达 RUNX2 的骨髓瘤细胞条件培养基降低成骨细胞活性并增加破骨细胞活性。在体内，骨髓瘤荷瘤小鼠的 RUNX2 表达与骨丢失呈正相关。这些结果表明，通过维持多发性骨髓瘤中成骨细胞和破骨细胞活性之间的平衡，抑制 RUNX2 的治疗可能有助于防止骨破坏。
