Tauroursodeoxycholic Acid Inhibits Neurogenic Heterotopic Ossification by Inducing Macrophage M2 Polarization and Upregulating IL-1β Secretion
10.11714/jsysu.med.YX20260063
- VernacularTitle:牛磺熊去氧胆酸通过诱导巨噬细胞M2极化上调IL-1β分泌抑制神经源性异位骨化
- Author:
Jiewen CHEN
1
;
Hongxi LAI
2
;
Yilong DENG
2
;
Tianjun CHEN
1
;
Shunying HUANG
1
;
Feng YE
1
;
Bingde ZHAO
1
;
Shudong CHEN
1
Author Information
1. Orthopedic Hospital of Guangdong Provincial Hospital of Chinese Medicine， Guangzhou University of Chinese Medicine， Guangzhou 510120，China
2. Department of Spine Surgery， The First Affiliated Hospital， Sun Yat-sen University， Guangzhou 510080，China
- Publication Type:Journal Article
- Keywords:
neurogenic heterotopic ossification;
spinal cord injury;
tauroursodeoxycholic acid;
M2 macrophage;
interleukin-1β
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2026;47(4):690-698
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the inhibitory effect of tauroursodeoxycholic acid （TUDCA） on neurogenic heterotopic ossification （NHO） after spinal cord injury and its potential mechanism. MethodsSPF-grade male C57BL/6 mice were used to establish an NHO model. The mice were randomly divided into three groups： sham operation group （laminectomy only）， NHO model group （spinal cord injury + intramuscular injection of cardiotoxin）， and TUDCA treatment group （NHO model + daily intragastric administration of TUDCA at 200 mg/kg for 4 consecutive weeks）. The area and maturity of heterotopic ossification were quantitatively assessed by micro-computed tomography（micro-CT） and hematoxylin-eosin（H&E） staining. Flow cytometry was used to quantify the interleukin（IL）-1β secretion level of M2 macrophages. RAW264.7 macrophages were cultured in vitro and divided into control， tumor necrosis factor（TNF）α， and TNFα+TUDCA （200 μmol/L） groups to detect the expression level of the polarization marker CD206. Additionally， macrophages were divided into control， TUDCA 200 μmol/L， and TUDCA 400 μmol/L groups to assess the IL-1β secretion level. ResultsCompared with the NHO group， the bone volume in the TUDCA-treated group was significantly reduced （12.69±1.13 vs. 7.647±1.19， P=0.003）. Compared with the TNFα group， qPCR results showed that the expression of the M2 macrophage marker CD206 was significantly upregulated in the TNFα+TUDCA group （0.55±0.019，1.11±0.023， P＜0.001）. Compared with the control group， ELISA results showed that TUDCA stimulation of macrophages significantly upregulated IL-1β secretion （404.7±24.38 vs. 652.8±32.61， P=0.003 7）. TUDCA administration upregulated IL-1β secretion by local muscle macrophages and inhibited heterotopic ossification formation. ConclusionsTUDCA might participate in inhibiting NHO formation by inducing M2 macrophage polarization and upregulating IL-1β secretion， thereby alleviating the development and progression of neurogenic heterotopic ossification after spinal cord injury. This finding provides experimental evidence for expanding the application of TUDCA in the treatment of complications following spinal cord injury.
