Liu Yang, Gao Gong-Ming, Yang Kai-Yuan, Nong Lu-Ming
Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, No.29 Xinglong Lane, Tianning District, Changzhou, Jiangsu Province 213000, P.R. China.
Dalian Medical University, No. 9 West Section of South Lvshun Road, Lvshunkou District, Dalian, Liaoning Province 116044, P.R. China.
iScience. 2022 May 13;25(6):104405. doi: 10.1016/j.isci.2022.104405. eCollection 2022 Jun 17.
Intervertebral disc (IVD) degeneration, which is common among elderly individuals, mainly manifests as low back pain and is caused by structural deterioration of the nucleus pulposus (NP) due to physiological mechanical stress. NP mesenchymal stem cells (NPMSCs) around the IVD endplate have multidirectional differentiation potential and can be used for tissue repair. To define favorable conditions for NPMSC proliferation and differentiation into chondroid cells for NP repair, the present study simulated periodic mechanical stress (PMS) of the NP under physiological conditions using MSC chondrogenic differentiation medium and recombinant human BMP-2 (rhBMP-2). rhBMP-2 effectively promoted NPMSC proliferation and differentiation. To clarify the mechanism of action of rhBMP-2, integrin alpha 1 (ITG A1) and BMP-2 were inhibited. PMS regulated the BMP-2/Smad1/RUNX2 pathway through ITG A1 and promoted NPMSC proliferation and differentiation. During tissue-engineered NP construction, PMS can effectively reduce osteogenic differentiation and promote extracellular matrix protein synthesis to enhance structural NP recovery.
椎间盘(IVD)退变在老年人中很常见,主要表现为腰痛,是由髓核(NP)因生理机械应力导致结构退变引起的。IVD终板周围的NP间充质干细胞(NPMSCs)具有多向分化潜能,可用于组织修复。为确定有利于NPMSC增殖并分化为软骨样细胞以修复NP的条件,本研究使用MSC软骨分化培养基和重组人骨形态发生蛋白-2(rhBMP-2)在生理条件下模拟NP的周期性机械应力(PMS)。rhBMP-2有效促进了NPMSC的增殖和分化。为阐明rhBMP-2的作用机制,对整合素α1(ITG A1)和BMP-2进行了抑制。PMS通过ITG A1调节BMP-2/Smad1/RUNX2通路,促进NPMSC的增殖和分化。在组织工程NP构建过程中,PMS可有效减少成骨分化并促进细胞外基质蛋白合成,以增强NP结构的恢复。