The Role of Microvascular Variations in the Process of Intervertebral Disk Degeneration and Its Regulatory Mechanisms: A Literature Review

• Published in: Orthopaedic surgery 2024-11, Vol.16 (11), p.2587-2597
• Main Authors: Zhang, Si‐Ping, Tong, Min, Li, Shi‐Da, Zhang, Bin, Zhang, Wenhao, Wang, Rong, Dong, Zhen‐Yu, Huang, Yi‐Fei
• Format: Article
• Language: English
• Subjects: Angiogenesis; annulus fibrosus; Cartilage; Collagen; endplates; intervertebral disk degeneration; microvasculature; nucleus pulposus; Nutrients; Review; Vascular endothelial growth factor
• ISSN: 1757-7853; 1757-7861
• DOI: 10.1111/os.14209

Microvascular changes are considered key factors in the process of intervertebral disk degeneration (IDD). Microvascular invasion and growth into the nucleus pulposus (NP) and cartilaginous endplates are unfavorable factors that trigger IDD. In contrast, the rich distribution of microvessels in the bony endplates and outer layers of the annulus fibrosus is an important safeguard for the nutrient supply and metabolism of the intervertebral disk (IVD). In particular, the adequate supply of microvessels in the bony endplates is the main source of the nutritional supply for the entire IVD. Microvessels can affect the progression of IDD through a variety of pathways. Many studies have explored the effects of microvessel alterations in the NP, annulus fibrosus, cartilaginous endplates, and bony endplates on the local microenvironment through inflammation, apoptosis, and senescence. Studies also elucidated the important roles of microvessel alterations in the process of IDD, as well as conducted in‐depth explorations of cytokines and biologics that can inhibit or promote the ingrowth of microvessels. Therefore, the present manuscript reviews the published literature on the effects of microvascular changes on IVD to summarize the roles of microvessels in IVD and elaborate on the mechanisms of action that promote or inhibit de novo microvessel formation in IVD. This review found that microvessels play an important role in the development of intervertebral disk degeneration (IDD), microvascular invasion within the nucleus pulposus (NP), and cartilage endplate (CEP) is an important factor contributing to IDD, whereas adequate microvascular distribution and blood supply in the bony endplate (BEP) is one of the key factors in maintaining the balance of nutrient supply and material metabolism in a healthy IVD. Multiple mechanisms and signaling pathways can influence microvascular alterations within the IVD, and microvascular proliferation or degradation within the IVD can in turn lead to the development and progression of IDD through multiple pathways. Although existing studies have made many advances in the mechanisms and triggers of IVD microvascularization, they still have more limitations. How to promote the improvement in functional microvessel density and blood flow in BEP and inhibit the proliferation of endothelial cells and microvessel growth in CEP and NP are still urgent challenges to be solved.