World journal of stem cells · 2025
Fat mass and obesity-associated protein in mesenchymal stem cells inhibits osteoclastogenesis via lnc NORAD/miR-4284 axis in ankylosing spondylitis.
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Liu Wen-Jie, Wang Jia-Xin, Li Quan-Feng, Zhang Yun-Hui, Ji Peng-Fei, Jin Jia-Hao, Zhang Yi-Bin, Yuan Zi-Hao, Feng Pei, Wu Yan-Feng, Shen Hui-Yong, Wang Peng
Аннотация
BACKGROUND: Ankylosing spondylitis (AS) is recognized as a long-term inflammatory disorder that leads to inflammation in the spine and joints, alongside abnormal bone growth. In previous studies, we reported that mesenchymal stem cells (MSCs) derived from individuals with AS demonstrated a remarkable inhibition in the formation of osteoclasts compared to those obtained from healthy donors. The mechanism through which MSCs from AS patients achieve this inhibition remains unclear.
AIM: To investigate the potential underlying mechanism by which MSCs from individuals with ankylosing spondylitis (AS-MSCs) inhibit osteoclastogenesis.
METHODS: We analysed fat mass and obesity-associated (FTO) protein levels in AS-MSCs and MSCs from healthy donors and investigated the effects and mechanism by which FTO in MSCs inhibits osteoclastogenesis by coculturing and measuring the levels of tartrate-resistant acid phosphatase, nuclear factor of activated T cells 1 and cathepsin K.
RESULTS: We found that FTO, an enzyme responsible for removing methyl groups from RNA, was more abundantly expressed in MSCs from AS patients than in those from healthy donors. Reducing FTO levels was shown to diminish the capacity of MSCs to inhibit osteoclast development. Further experimental results revealed that FTO affects the stability of the long non-coding RNA activated by DNA damage (NORAD) by altering its N6-methyladenosine methylation status. Deactivating NORAD in MSCs significantly increased osteoclast formation by affecting miR-4284, which could regulate the MSC-mediated inhibition of osteoclastogenesis reported in our previous research.
CONCLUSION: This study revealed elevated FTO levels in AS-MSCs and found that FTO regulated the ability of AS-MSCs to inhibit osteoclast formation through the long noncoding RNA NORAD/miR-4284 axis.
AIM: To investigate the potential underlying mechanism by which MSCs from individuals with ankylosing spondylitis (AS-MSCs) inhibit osteoclastogenesis.
METHODS: We analysed fat mass and obesity-associated (FTO) protein levels in AS-MSCs and MSCs from healthy donors and investigated the effects and mechanism by which FTO in MSCs inhibits osteoclastogenesis by coculturing and measuring the levels of tartrate-resistant acid phosphatase, nuclear factor of activated T cells 1 and cathepsin K.
RESULTS: We found that FTO, an enzyme responsible for removing methyl groups from RNA, was more abundantly expressed in MSCs from AS patients than in those from healthy donors. Reducing FTO levels was shown to diminish the capacity of MSCs to inhibit osteoclast development. Further experimental results revealed that FTO affects the stability of the long non-coding RNA activated by DNA damage (NORAD) by altering its N6-methyladenosine methylation status. Deactivating NORAD in MSCs significantly increased osteoclast formation by affecting miR-4284, which could regulate the MSC-mediated inhibition of osteoclastogenesis reported in our previous research.
CONCLUSION: This study revealed elevated FTO levels in AS-MSCs and found that FTO regulated the ability of AS-MSCs to inhibit osteoclast formation through the long noncoding RNA NORAD/miR-4284 axis.