后韧带损伤诱导恒河猴进行性关节强直样结构重塑
Posterior ligamentous injury induces progressive ankylosis-like structural remodeling in rhesus macaques.
Posterior ligamentous injury induces progressive ankylosis-like structural remodeling in rhesus macaques.
强直性脊柱炎(AS)的结构性进展难以在具有与人类相关脊柱解剖结构和长期影像学读出数据的物种中建模。在此,我们通过标准化的后路L2-L6肌肉韧带损伤建立了AS样结构重塑的恒河猴模型,并以假手术动物作为阴性对照。进行了长达50个月的纵向CT/MRI评估,并辅以离体micro-CT和全切片组织学检查。模型动物出现了累积性结构改变,从早期局灶性附着点/软骨下重塑进展为后部骨化、节段性桥接、骶髂关节结构受累及晚期强直样重塑,而假手术动物未显示典型的AS样结构病变。基于CT的半定量评估显示结构负荷随时间进行性增加,并表明后部结构是促成终末强直样表型的主要解剖区域。全切片组织学进一步支持从后部和椎间盘周围纤维化重塑到晚期纤维骨性改变的组织水平连续谱,与影像学所定义的从局灶性重塑到桥接和结构固定的进展相一致。这些发现表明,恒河猴后部肌肉韧带损伤可驱动长期、可量化的AS样结构重塑,并提示后部肌肉韧带复合体是连接局部损伤修复、纤维化、纤维骨性转化和强直样进展的潜在解剖学和组织学枢纽。
Structural progression in ankylosing spondylitis (AS) is difficult to model in species with human-relevant spinal anatomy and long-term imaging readouts. Here, we established a rhesus macaque model of AS-like structural remodeling by standardized posterior L2-L6 musculoligamentous injury, with sham-operated animals serving as negative controls. Longitudinal CT/MRI assessment was performed for up to 50 months, supplemented by ex vivo micro-CT and whole-section histology. Model animals developed cumulative structural changes that progressed from early focal entheseal/subchondral remodeling to posterior ossification, segmental bridging, sacroiliac joint structural involvement, and late ankylosis-like remodeling, whereas sham animals showed no typical AS-like structural lesions. CT-based semiquantitative assessment demonstrated a progressive increase in structural burden over time and indicated that posterior elements were the dominant anatomical domain contributing to the terminal ankylosis-like phenotype. Whole-section histology further supported a tissue-level continuum from posterior and peri-discal fibrotic remodeling to late fibro-osseous change, consistent with the imaging-defined progression from focal remodeling to bridging and structural fixation. These findings show that posterior musculoligamentous injury in rhesus macaques can drive long-term, quantifiable, AS-like structural remodeling and nominate the posterior musculoligamentous complex as a potential anatomical and histological hub linking local injury repair, fibrosis, fibro-osseous transition, and ankylosis-like progression.
Yue Chen, Xiaorong Sun, Dan Su, Feng Luo, Min Zhang, Yuwei Xu, et al. Posterior ligamentous injury induces progressive ankylosis-like structural remodeling in rhesus macaques.. Biochemical and biophysical research communications. 2026; doi:10.1016/j.bbrc.2026.154089.
Yue Chen, Xiaorong Sun, Dan Su, Feng Luo, Min Zhang, Yuwei Xu, et al (2026). Posterior ligamentous injury induces progressive ankylosis-like structural remodeling in rhesus macaques.. Biochemical and biophysical research communications. https://doi.org/10.1016/j.bbrc.2026.154089
Yue Chen, Xiaorong Sun, Dan Su, Feng Luo, Min Zhang, Yuwei Xu, et al. Posterior ligamentous injury induces progressive ankylosis-like structural remodeling in rhesus macaques.[J]. Biochemical and biophysical research communications, 2026 doi:10.1016/j.bbrc.2026.154089.
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