期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ijms23126421
关键词
osteoclast; fusion; Calcrl; Marco; Ube3a; CRISPR-Cas9
资金
- Korea Mouse Phenotyping Project of the Ministry of Science and ICT through the National Research Foundation [2014M3A9D5A01073658]
- Commercializations Promotion Agency for R&D Outcomes (COMPA) - Korean government (MSIT) [2021C200]
- National Research Foundation of Korea [2014M3A9D5A01073658] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Science & Technology Job Promotion Agency, Republic of Korea [2021C200] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
In this study, the fusion-specific genes involved in osteoclastogenesis were identified using RNA sequencing and confirmed their importance through gene editing. These findings provide potential targets for osteoporosis therapy.
Osteoclasts are derived from hematopoietic stem cells. Monocyte preosteoclasts obtain resorbing activity via cell-cell fusion to generate multinucleated cells. However, the mechanisms and molecules involved in the fusion process are poorly understood. In this study, we performed RNA sequencing with single nucleated cells (SNCs) and multinucleated cells (MNCs) to identify the fusion-specific genes. The SNCs and MNCs were isolated under the same conditions during osteoclastogenesis with the receptor activator of nuclear factor-kappa B ligand (RANKL) administration. Based on this analysis, the expression of seven genes was found to be significantly increased in MNCs but decreased in SNCs, compared to that in bone marrow-derived macrophages (BMMs). We then generated knockout macrophage cell lines using a CRISPR-Cas9 genome-editing tool to examine their function during osteoclastogenesis. Calcrl-, Marco-, or Ube3a-deficient cells could not develop multinucleated giant osteoclasts upon RANKL stimulation. However, Tmem26-deficient cells fused more efficiently than control cells. Our findings demonstrate that Calcrl, Marco, and Ube3a are novel determinants of osteoclastogenesis, especially with respect to cell fusion, and highlight potential targets for osteoporosis therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据