Scholarlink

<p>Multiple Myeloma bone disease (MMBD) is highly prevalent in the multiple myeloma (MM) patients. Using the patients’ gene expression profile, we identified Rho Family GTPase 3 (RND3) as a gene whose expression in MM negatively associated with MMBD severity. Using MM patients’ biopsies, we validated that the patients with MMBD had decreased RND3 expression, compared with the patients without MMBD. To investigate the function of RND3 in MMBD, we established RND3 knocking down (RN-KD) MM cells, as well as control knock down (CT-KD). In a human MM xenograft mouse model, RN-KD MM caused severer MMBD than CT-KD. RN-KD MM promoted osteoclast (OC) differentiation, while inhibited osteoblast (OB) maturation. Mechanistically, RND3 interacted with ROCKs, Rho-associated kinases, in MM cells. ROCK family kinases included ROCK1 and ROCK2. In OC regulation, RND3 interacted with ROCK1 and ROCK2, exerted influence on Smad2/3 activation, which in turn controlled the downstream MMP-9, a known MM-secreted OC regulatory factor. In OB regulation, RND3 interacted with ROCK2, and regulated STAT3, which had downstream factor DKK1, a pivotal MM-secreted OB regulator in context of MM. Pan-ROCK inhibitor Y-27,632, which inhibited both ROCK1 and 2, decreased MMP-9 and DKK1 expressions in MM, and showed effective in MMBD treatment in vivo in the MM mouse model. Overall, our data suggested that intra-MM RND3-ROCK1/2 axis affected both OC and OB regulatory cytokines’ expression from MM cells.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Rho-related GTP-binding protein RhoE (RND3) regulates multiple myeloma bone disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月7日

查看全文
  • Qianwen Gao,
  • Wenjiao Tang,
  • Ziyue Mi,
  • Siyao He,
  • Haonan Yang,
  • Fangfang Wang,
  • Jingcao Huang,
  • Yue Zhang,
  • Jingjing Wen,
  • Linfeng Li,
  • Hongmei Luo,
  • Xiang Liu,
  • Xinyu Zhai,
  • Xiaohui Zhao,
  • Li Zhang,
  • Ting Niu,
  • Yuhuan Zheng

摘要

Multiple Myeloma bone disease (MMBD) is highly prevalent in the multiple myeloma (MM) patients. Using the patients’ gene expression profile, we identified Rho Family GTPase 3 (RND3) as a gene whose expression in MM negatively associated with MMBD severity. Using MM patients’ biopsies, we validated that the patients with MMBD had decreased RND3 expression, compared with the patients without MMBD. To investigate the function of RND3 in MMBD, we established RND3 knocking down (RN-KD) MM cells, as well as control knock down (CT-KD). In a human MM xenograft mouse model, RN-KD MM caused severer MMBD than CT-KD. RN-KD MM promoted osteoclast (OC) differentiation, while inhibited osteoblast (OB) maturation. Mechanistically, RND3 interacted with ROCKs, Rho-associated kinases, in MM cells. ROCK family kinases included ROCK1 and ROCK2. In OC regulation, RND3 interacted with ROCK1 and ROCK2, exerted influence on Smad2/3 activation, which in turn controlled the downstream MMP-9, a known MM-secreted OC regulatory factor. In OB regulation, RND3 interacted with ROCK2, and regulated STAT3, which had downstream factor DKK1, a pivotal MM-secreted OB regulator in context of MM. Pan-ROCK inhibitor Y-27,632, which inhibited both ROCK1 and 2, decreased MMP-9 and DKK1 expressions in MM, and showed effective in MMBD treatment in vivo in the MM mouse model. Overall, our data suggested that intra-MM RND3-ROCK1/2 axis affected both OC and OB regulatory cytokines’ expression from MM cells.