Emanuel J. Novais, Rajkishen Narayanan, Jose A. Canseco, Koen van de Wetering, Christopher K. Kepler, Alan S. Hilibrand, Alexander R. Vaccaro, Makarand V. Risbud
{"title":"A new perspective on intervertebral disc calcification—from bench to bedside","authors":"Emanuel J. Novais, Rajkishen Narayanan, Jose A. Canseco, Koen van de Wetering, Christopher K. Kepler, Alan S. Hilibrand, Alexander R. Vaccaro, Makarand V. Risbud","doi":"10.1038/s41413-023-00307-3","DOIUrl":null,"url":null,"abstract":"<p>Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics: hypertrophic chondrocyte-like cell differentiation; TNAP, ENPP1, and ANK upregulation; cell death; altered Pi and PPi homeostasis; and local inflammation. Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype. It is essential to recognize that the presentation and nature of mineralization differ between AF, NP, and EP compartments. Moreover, the combination of anatomic location, genetics, and environmental stressors, such as aging or trauma, govern the predisposition to calcification. Lastly, the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis, along with disc cell death and differentiation status. While there is limited understanding of this phenotype, understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":14.3000,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bone Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41413-023-00307-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0
Abstract
Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics: hypertrophic chondrocyte-like cell differentiation; TNAP, ENPP1, and ANK upregulation; cell death; altered Pi and PPi homeostasis; and local inflammation. Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype. It is essential to recognize that the presentation and nature of mineralization differ between AF, NP, and EP compartments. Moreover, the combination of anatomic location, genetics, and environmental stressors, such as aging or trauma, govern the predisposition to calcification. Lastly, the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis, along with disc cell death and differentiation status. While there is limited understanding of this phenotype, understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.
椎间盘退变是导致慢性腰痛和颈痛的主要原因。因此,迫切需要了解椎间盘退变的各种表型,如纤维化、异位钙化、椎间盘突出或混合表型。在这些表型中,对椎间盘钙化的研究最少。异位钙化顾名思义是软组织的病理性矿化,在血管、皮肤和软骨的病变中被广泛研究。在临床上,椎间盘钙化与手术效果不佳和保守治疗无效的背痛有关。椎间盘钙化通常是椎间盘老化和进行性退变的结果,但具有独特的分子和形态学特征:肥大软骨细胞样细胞分化;TNAP、ENPP1 和 ANK 上调;细胞死亡;Pi 和 PPi 平衡改变;局部炎症。最近对小鼠模型的研究使人们对这种表型的机制有了更好的了解。必须认识到,AF、NP 和 EP 区间矿化的表现形式和性质各不相同。此外,解剖位置、遗传和环境压力因素(如衰老或创伤)共同作用,导致钙化倾向。最后,钙和π代谢的系统调控不如由ANK-ENPP1轴调控的PPi局部活性以及椎间盘细胞死亡和分化状态重要。虽然对这种表型的了解还很有限,但了解支配椎间盘局部钙化的分子途径可能有助于开发疾病调节药物和更好地临床治疗退变相关病症。
期刊介绍:
Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.