Spinal hypermobility accelerates ossification in posterior longitudinal ligaments: insights from an in vivo mouse model
IntroductionOssification of the posterior longitudinal ligaments (OPLL) is characterized by heterotopic ossification in the posterior longitudinal ligament of spine. Our earlier research found that mechanical stimulation enhances osteogenic differentiation in OPLL-derived ligament cells. Nevertheles...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2025.1561199/full |
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| author | Tao Tang Tao Tang Zhengya Zhu Zhengya Zhu Zhongyuan He Zhongyuan He Fuan Wang Lin Chen Jianfeng Li Hongkun Chen Jiaxiang Zhou Jianmin Wang Shaoyu Liu Yunfeng Yao Xizhe Liu Zhiyu Zhou |
| author_facet | Tao Tang Tao Tang Zhengya Zhu Zhengya Zhu Zhongyuan He Zhongyuan He Fuan Wang Lin Chen Jianfeng Li Hongkun Chen Jiaxiang Zhou Jianmin Wang Shaoyu Liu Yunfeng Yao Xizhe Liu Zhiyu Zhou |
| author_sort | Tao Tang |
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| description | IntroductionOssification of the posterior longitudinal ligaments (OPLL) is characterized by heterotopic ossification in the posterior longitudinal ligament of spine. Our earlier research found that mechanical stimulation enhances osteogenic differentiation in OPLL-derived ligament cells. Nevertheless, the function of hypermobility of the spine on ligament ossification remain unexplored in vivo.MethodsWe created the novel stimulation device to induce spinal hypermobility in mice with heterotopic ossification of the spine ligaments. The mice were randomly divided into three groups, control, slow hypermobility (SH) group and fast hypermobility (FH) group according to the frequency of spinal movement. Ligament ossification and changes in spinal range of motion (ROM) were assessed using micro-CT and X-rays. Morphological alterations were examined through HE staining. Behavioral evaluation was performed using the Basso Mouse Scale (BMS) score and inclined plane test (IPT). Immunofluorescence was employed to examine the expression of related proteins.ResultsAfter 8 weeks, it showed increased ligament ossification and chondrocyte proliferation both in SH and FH group. After 16 weeks, The BMS score and IPT were lower both in the SH and FH group compared to the controls. Additionally, the ROM of cervicothoracic and thoracolumbar spine was lower in the FH group than in the controls. Immunofluorescence analysis revealed increased levels of SP7, RUNX2, OCN, DLX5, NOTCH1, and HES1 in the ligament tissues of the FH group compared to controls.Conclusionspinal hypermobility promotes the progression of ossification in mice with heterotopic ossification of the spine, shedding new light on the pathogenesis of OPLL. |
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| institution | OA Journals |
| issn | 1664-042X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj-art-980d982c52844da387d124b69fd62f012025-08-20T02:07:20ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-03-011610.3389/fphys.2025.15611991561199Spinal hypermobility accelerates ossification in posterior longitudinal ligaments: insights from an in vivo mouse modelTao Tang0Tao Tang1Zhengya Zhu2Zhengya Zhu3Zhongyuan He4Zhongyuan He5Fuan Wang6Lin Chen7Jianfeng Li8Hongkun Chen9Jiaxiang Zhou10Jianmin Wang11Shaoyu Liu12Yunfeng Yao13Xizhe Liu14Zhiyu Zhou15Department of Orthopedic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Orthopaedics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaGuangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaIntroductionOssification of the posterior longitudinal ligaments (OPLL) is characterized by heterotopic ossification in the posterior longitudinal ligament of spine. Our earlier research found that mechanical stimulation enhances osteogenic differentiation in OPLL-derived ligament cells. Nevertheless, the function of hypermobility of the spine on ligament ossification remain unexplored in vivo.MethodsWe created the novel stimulation device to induce spinal hypermobility in mice with heterotopic ossification of the spine ligaments. The mice were randomly divided into three groups, control, slow hypermobility (SH) group and fast hypermobility (FH) group according to the frequency of spinal movement. Ligament ossification and changes in spinal range of motion (ROM) were assessed using micro-CT and X-rays. Morphological alterations were examined through HE staining. Behavioral evaluation was performed using the Basso Mouse Scale (BMS) score and inclined plane test (IPT). Immunofluorescence was employed to examine the expression of related proteins.ResultsAfter 8 weeks, it showed increased ligament ossification and chondrocyte proliferation both in SH and FH group. After 16 weeks, The BMS score and IPT were lower both in the SH and FH group compared to the controls. Additionally, the ROM of cervicothoracic and thoracolumbar spine was lower in the FH group than in the controls. Immunofluorescence analysis revealed increased levels of SP7, RUNX2, OCN, DLX5, NOTCH1, and HES1 in the ligament tissues of the FH group compared to controls.Conclusionspinal hypermobility promotes the progression of ossification in mice with heterotopic ossification of the spine, shedding new light on the pathogenesis of OPLL.https://www.frontiersin.org/articles/10.3389/fphys.2025.1561199/fullOPLLheterotopic ossificationspinal hypermobilityanimal modelsspinal cord compression |
| spellingShingle | Tao Tang Tao Tang Zhengya Zhu Zhengya Zhu Zhongyuan He Zhongyuan He Fuan Wang Lin Chen Jianfeng Li Hongkun Chen Jiaxiang Zhou Jianmin Wang Shaoyu Liu Yunfeng Yao Xizhe Liu Zhiyu Zhou Spinal hypermobility accelerates ossification in posterior longitudinal ligaments: insights from an in vivo mouse model Frontiers in Physiology OPLL heterotopic ossification spinal hypermobility animal models spinal cord compression |
| title | Spinal hypermobility accelerates ossification in posterior longitudinal ligaments: insights from an in vivo mouse model |
| title_full | Spinal hypermobility accelerates ossification in posterior longitudinal ligaments: insights from an in vivo mouse model |
| title_fullStr | Spinal hypermobility accelerates ossification in posterior longitudinal ligaments: insights from an in vivo mouse model |
| title_full_unstemmed | Spinal hypermobility accelerates ossification in posterior longitudinal ligaments: insights from an in vivo mouse model |
| title_short | Spinal hypermobility accelerates ossification in posterior longitudinal ligaments: insights from an in vivo mouse model |
| title_sort | spinal hypermobility accelerates ossification in posterior longitudinal ligaments insights from an in vivo mouse model |
| topic | OPLL heterotopic ossification spinal hypermobility animal models spinal cord compression |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2025.1561199/full |
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