Department of Orthopaedics, The Third Xiangya Hospital of Central South University, 138 Tongzipo Rd, Changsha, Hunan, 410013, China.
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Cell Tissue Res. 2023 Jul;393(1):97-109. doi: 10.1007/s00441-023-03751-z. Epub 2023 Apr 13.
Excessive apoptosis of intervertebral disc cells, namely nucleus pulposus (NP) cells, results in decreased cell density and extracellular matrix (ECM) catabolism, hence leading to intervertebral disc degeneration (IVDD). As a cell model in the present study, a commercially available human NP cell line was utilized. Long noncoding RNAs and microRNAs may regulate the proliferation or apoptosis of human NP cells, hence exerting a significant influence on the occurrence of IVDD. KLF3-AS1 was discovered to be abnormally downregulated in IVDD tissues. Overexpression of KLF3-AS1 enhanced NP cell viability, prevented cell apoptosis, boosted ECM synthesis, and lowered MMP-13 and ADAMTS4 levels. ZBTB20 and KLF3-AS1 were co-expressed in IVDD; ZBTB20 overexpression had similar effects on NP cells, ECM production, and MMP-13 and ADAMTS4 levels as KLF3-AS1 overexpression. miR-10a-3p may target KLF3-AS1 and ZBTB20 and inhibit the expression of ZBTB20. Inhibition of miR-10a-3p enhanced NP cell viability, reduced apoptosis, and enhanced ECM synthesis. KLF3-AS1 overexpression increased ZBTB20 expression, whereas miR-10a-3p overexpression decreased ZBTB20 expression; miR-10a-3p overexpression reduced the effects of KLF3-AS1 on ZBTB20. Overexpression of miR-10a-3p consistently decreased the effects of KLF3-AS1 overexpression on NP cell survival, apoptosis, and ECM synthesis. In conclusion, KLF3-AS1 overexpression may ameliorate degenerative NP cell alterations through the miR-10a-3p/ZBTB20 axis.
椎间盘细胞（即髓核细胞）的过度凋亡会导致细胞密度降低和细胞外基质（ECM）的分解代谢，从而导致椎间盘退变（IVDD）。在本研究中，使用了一种商业上可获得的人 NP 细胞系作为细胞模型。长链非编码 RNA 和 microRNAs 可能调节人 NP 细胞的增殖或凋亡，从而对 IVDD 的发生产生重大影响。在 IVDD 组织中发现 KLF3-AS1 异常下调。过表达 KLF3-AS1 可增强 NP 细胞活力，阻止细胞凋亡，促进 ECM 合成，并降低 MMP-13 和 ADAMTS4 水平。在 IVDD 中 ZBTB20 和 KLF3-AS1 共同表达；过表达 ZBTB20 对 NP 细胞、ECM 产生以及 MMP-13 和 ADAMTS4 水平的影响与过表达 KLF3-AS1 相似。miR-10a-3p 可能靶向 KLF3-AS1 和 ZBTB20 并抑制 ZBTB20 的表达。抑制 miR-10a-3p 可增强 NP 细胞活力，减少凋亡并增强 ECM 合成。过表达 KLF3-AS1 增加 ZBTB20 的表达，而过表达 miR-10a-3p 则降低 ZBTB20 的表达；miR-10a-3p 过表达降低了 KLF3-AS1 对 ZBTB20 的作用。过表达 miR-10a-3p 始终降低了 KLF3-AS1 过表达对 NP 细胞存活、凋亡和 ECM 合成的影响。总之，KLF3-AS1 的过表达可能通过 miR-10a-3p/ZBTB20 轴改善退行性 NP 细胞的改变。
