REVIEW article
Front. Cell Dev. Biol.
Sec. Signaling
Angiogenesis in ossification of the posterior longitudinal ligament: progress from mechanism to targeted intervention
Provisionally accepted
Xiaoyu Liu1
Xiaomin Wang1
Kangyi Hu1
Haonan Wen2
Lu Liu1Haoxing Li1Zhixin Che1Ting Song1Jinquan Lai2Min Song1*Yongjia Song1*- 1Gansu University of Chinese Medicine, Lanzhou, China
- 2Shenzhen Luohu Hospital of Traditional Chinese Medicine, Shenzhen, China
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Ossification of the posterior longitudinal ligament (OPLL) is a degenerative spinal disorder characterized by heterotopic ossification of ligamentous tissue. Its pathogenesis is multifactorial and complex, involving genetic susceptibility, chronic inflammation, mechanical stress, and metabolic dysregulation. In recent years, accumulating evidence has demonstrated that angiogenesis not only supplies essential nutrients and metabolic support to ossified ligament regions but also actively regulates the differentiation of mesenchymal stem cells toward osteogenic and chondrogenic lineages through specific molecular signaling pathways, thereby promoting ectopic bone formation. Focusing on angiogenesis as a central theme, this review systematically summarizes the mechanisms by which key molecules, including LOXL2, Sema3A, integrin αVβ3, ANGPT2, IL-6, TGF-β, the ACE D/D polymorphism, and YAP, mediate the coupling of angiogenesis and osteogenesis in OPLL. Furthermore, we propose angiogenesis-targeted strategies as a potential therapeutic avenue for OPLL, aiming to provide new theoretical insights and directions for both basic research and clinical intervention.
Keywords: Angiogenesis, Angiogenesis -osteogenesis coupling, Ossification of the posterior longitudinal ligament, signaling pathway, targeted intervention
Received: 17 Sep 2025; Accepted: 03 Feb 2026.
Copyright: © 2026 Liu, Wang, Hu, Wen, Liu, Li, Che, Song, Lai, Song and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Min Song
Yongjia Song
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