RUNX2 promotes the suppression of osteoblast function and enhancement of osteoclast activity by multiple myeloma cells.
RUNX2 promotes the suppression of osteoblast function and enhancement of osteoclast activity by multiple myeloma cells.
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DOI：
10.1007/s12032-023-01960-8
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发表时间：
2023-03-10
期刊：
影响因子：
3.4
通讯作者：
Li, Juan
中科院分区：
文献类型：
--
作者：
Huang, Beihui;Liu, Huixin;Chan, Szehoi;Liu, Junru;Gu, Jingli;Chen, Meilan;Kuang, Lifen;Li, Xiaozhe;Zhang, Xingding;Li, Juan
RUNX 2是一种参与成骨细胞分化和软骨细胞成熟的转录因子，在肿瘤的侵袭和转移中起重要作用。随着研究的深入，有证据表明RUNX 2与癌症中的骨破坏相关。然而，其在多发性骨髓瘤中的作用机制仍不清楚。通过观察骨髓瘤细胞条件培养液对前成骨细胞（MC 3 T3-E1）和前破骨细胞（RAW264.7）的诱导作用以及骨髓瘤荷瘤小鼠的构建，我们发现RUNX 2促进多发性骨髓瘤的骨破坏。在体外，来自RUNX 2过表达骨髓瘤细胞的条件培养基降低了成骨细胞活性，增加了破骨细胞活性。在体内，RUNX 2表达与骨髓瘤小鼠的骨丢失呈正相关。这些结果表明，治疗性抑制RUNX 2可以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来防止骨破坏。
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.
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