The Role of Collagen Matrix in the Development and Progression of Heterotopic Ossification in Tendon and Its Biological Mechanisms

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

The FASEB Journal Pub Date : 2025-07-21 DOI:10.1096/fj.202501170RR

Chenxi Ren, Fa Liu, Shuyang Zhang, Huiyun Xu, Pengfei Yang

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Abstract

As the primary force-transmitting structure in the musculoskeletal system, tendons are susceptible to collagen fiber disorganization and microenvironmental alterations following mechanical overload or traumatic injury. The aberrant mineralization cascade ultimately culminates in heterotopic ossification (HO), wherein heterotopic bone forms through dysregulated osteogenic processes. Current therapeutic paradigms for tendon HO remain palliative rather than curative, underscoring critical knowledge gaps in its etiopathogenesis. Therefore, the present review paper systematically examines emerging evidence on the synergistic interplay between damaged collagen architecture and ionic/protein microenvironment changes in driving HO progression, with particular emphasis on how collagen ultrastructural defects serve as mineralization templates through stereochemical nucleation, and microenvironmental ionic/protein alterations that amplify osteochondrogenic differentiation. The mechanistic framework of HO elucidated in the present paper would further contribute to novel strategies development for the prevention and treatment of pathological mineralization in tendon.

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胶原基质在肌腱异位骨化发生进展中的作用及其生物学机制

作为肌肉骨骼系统中主要的力传递结构，肌腱在机械负荷或创伤性损伤后容易受到胶原纤维的破坏和微环境的改变。异常矿化级联最终导致异位骨化（HO），其中异位骨通过失调的成骨过程形成。目前肌腱HO的治疗模式仍然是姑息性的，而不是治愈性的，这强调了其发病机制的关键知识空白。因此，本综述系统地研究了损伤的胶原结构和离子/蛋白质微环境变化之间的协同相互作用在驱动HO进展中的新证据，特别强调胶原超微结构缺陷如何通过立体化学成核作为矿化模板，以及微环境离子/蛋白质改变如何放大骨软骨生成分化。本文所阐明的HO的机制框架将进一步有助于开发预防和治疗肌腱病理性矿化的新策略。

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来源期刊

The FASEB Journal 生物-生化与分子生物学

CiteScore

9.20

自引率

2.10%

发文量

6243

审稿时长

3 months

期刊介绍： The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.