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.

椎间盘退变主要导致慢性腰背和颈部疼痛。因此，迫切需要了解椎间盘退变表型的范围，例如纤维化、异位钙化、突出或混合表型。在这些表型中，椎间盘钙化研究最少。根据定义，异位钙化是软组织的病理矿化，在影响脉管系统、皮肤和软骨的情况下得到广泛研究。临床上，椎间盘钙化与手术效果不佳和保守治疗难治的背痛有关。它经常被视为椎间盘老化和进行性退变的结果，但表现出独特的分子和形态学特征：肥大的软骨细胞样细胞分化；TNAP、ENPP1 和 ANK 上调；细胞死亡；改变 Pi 和 PPi 稳态；以及局部炎症。最近对小鼠模型的研究使人们更好地了解了这种表型背后的机制。必须认识到 AF、NP 和 EP 区室之间矿化的表现和性质有所不同。此外，解剖位置、遗传和环境压力因素（例如衰老或创伤）的结合控制着钙化的倾向。最后，钙和 Pi 代谢的全身调节不如 ANK-ENPP1 轴调节的 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有限，但了解控制局部椎间盘钙化的分子途径可能会导致开发缓解疾病的药物以及更好地对退变相关病理进行临床管理。