Cyclic Tensile Stress to Rat Thoracolumbar Ligamentum Flavum Inducing the Ossification of Ligamentum Flavum

Abstract

Study Design. Western blot, reverse transcription-polymerase chain reaction (RT-PCR), radiological, and histological analyses of the rat ossification of ligamentum flavum (OLF) induced by cyclic tensile stress.Objective. The aim of this study was to induce the OLF using cyclic tensile stress to rat thoracolumbar ligamentum flavum, and to investigate the possible molecular mechanism of tensioninduced OLF. Summary of Background Data. Tensile stress has been considered as an important factor leading to the OLF. So far, however, no OLF induced by tension has been reported. Methods. Forty rats were randomly divided into five equal groups. For control groups, the blank and anesthesia groups were not subjected to tension. For experimental groups, the 4-, 8-, and 12-week groups were subjected to cyclic tensile stress of ligamentum flavum after abdominal anesthesia for 4 weeks, 8 weeks, and 12 weeks, respectively, using an original stress apparatus for rats. The radiological and morphological changes of rat spine, as well as the protein and mRNA expressions of CD44, bone morphogenetic protein-2 (BMP-2), integrin b3, collagen protein type I (COL1), osteopontin (OPN), runt-related transcription factor 2 (RUNX-2), and vascular endothelial growth factor (VEGF), were concerned. Results. The micro-CT showed OLF in the 4-, 8-, and 12-week group. The axial maximum occupied area of ossifications was 1.42 mm 2 , 3.35 mm 2 , and 7.28 mm 2 , respectively. In histopathology, chondrocytes proliferated in the experimental model; woven bone arose in the 8-and 12-week groups, and was more noticeable in the 12-week group. According to western blot and RT-PCR, the expressions of seven osteogenesis-related molecules were all increased in three experimental groups. Conclusion. Cyclic tensile stress to the ligamentum flavum in rats can induce the OLF, and the longer the duration, the more visible the osteogenesis. The upregulation and synergism of osteogenesis-related molecules may contribute to the OLF induced by tensile stress.

Uniaxial cyclic stretch enhances osteogenic differentiation of OPLL-derived primary cells via YAP-Wnt/β-catenin axis

“…Clinical reports showed that in comparison with stand-alone laminoplasty, cervical laminoplasty combined instrumented fusion suppresses the progression of OPLL (Kang et al, 2019;Katsumi et al, 2016;Lee et al, 2017). In vivo experiments in animal models resulted in a similar conclusion: when rat tail or thoracic vertebra are subjected to repeated excessive traction stimulation, heterotopic ossification of local ligaments occurs (Tsukamoto et al, 2006;Zhao et al, 2021). Although these clinical features have been described in detail, the specific molecular mechanism remains to be elucidated.…”

High Systemic Immune-Inflammation Index and Body Mass Index Are Independent Risk Factors of the Thoracic Ossification of the Ligamentum Flavum

“…Thoracic OLF has been considered as a multifactorial disease, and several pathogenic factors, including genetic inheritance, metabolic disorders, inflammation, and mechanical stress, contribute to its onset and development [5][6][7]. Several studies have been conducted to identify the risk factors of thoracic OLF to further explore its underlying mechanisms [8][9][10][11][12].…”

Safety and efficacy of one-hole split endoscope technique for surgical treatment of thoracic ossification of the ligamentum flavum

“…In line with prior studies, our investigation revealed that 8 out of 13 cases (61.5%) manifested below the T9 segment. This occurrence may be attributed to factors such as spinal mobility and mechanical stress 5 , 18 . While there remains no universal consensus on the treatment principles of TOLF, existing studies strongly suggest that conservative therapy is inadequate in averting spinal cord compression-related complications.…”