Construction of tissue-engineered nucleus pulposus by stimulation with periodic mechanical stress and BMP-2

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.