Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Sports Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Connect Tissue Res. 2023 Jul;64(4):310-322. doi: 10.1080/03008207.2022.2160327. Epub 2023 Jan 4.
Degenerative changes in the spinal ligaments, such as hypertrophy or ossification, are important pathophysiological mechanisms of secondary spinal stenosis and neurological compression. Extracellular matrix (ECM) remodeling is one of the major pathological changes in ligament degeneration, and in this remodeling, ECM proteinase-mediated degradation of elastin and collagen plays a vital role. Zinc-dependent endopeptidases, including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and ADAMs with thrombospondin-1 motifs (ADAMTSs) are key factors in ECM remodeling. This review aims to elucidate the underlying mechanisms of these metalloproteinases in the initiation and progression of spinal ligament degeneration.
We clarify current literature on the dysregulation of MMPs/ADAMs/ADAMTS and their endogenous inhibitors in degenerative spinal ligament diseases. In addition, some instructive information was excavated from the raw data of the relevant high-throughput analysis.
The dysregulation of metalloproteinases and their endogenous inhibitors may affect ligament degeneration by involving several interrelated processes, represented by ECM degradation, fibroblast proliferation, and osteogenic differentiation. Antagonists of the key targets of the processes may in turn ease ligament degeneration.
脊柱韧带的退行性改变，如肥大或骨化，是继发性椎管狭窄和神经压迫的重要病理生理机制。细胞外基质（ECM）重塑是韧带退变的主要病理变化之一，在这种重塑中，ECM 蛋白水解酶介导的弹性蛋白和胶原蛋白的降解起着至关重要的作用。锌依赖性内肽酶，包括基质金属蛋白酶（MMPs）、解整合素和金属蛋白酶（ADAMs）以及含血栓反应蛋白-1 基序的 ADAMs（ADAMTSs），是 ECM 重塑的关键因素。本综述旨在阐明这些金属蛋白酶在脊柱韧带退变的发生和进展中的潜在机制。
我们阐明了关于 MMPs/ADAMs/ADAMTS 及其在退行性脊柱韧带疾病中的内源性抑制剂失调的当前文献。此外，还从相关高通量分析的原始数据中挖掘了一些有启发性的信息。
金属蛋白酶及其内源性抑制剂的失调可能通过涉及几个相互关联的过程来影响韧带退化，这些过程表现为 ECM 降解、成纤维细胞增殖和成骨分化。这些过程的关键靶点的拮抗剂反过来可能缓解韧带退化。
