Format

Send to

Choose Destination
Biochim Biophys Acta. 2016 Aug;1863(8):1961-8. doi: 10.1016/j.bbamcr.2016.05.004. Epub 2016 May 6.

Mesenchymal stem cells regulate mechanical properties of human degenerated nucleus pulposus cells through SDF-1/CXCR4/AKT axis.

Author information

1
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
2
Department of Ophthalmology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
3
Department of Orthopedics, General Hospital of Chinese PLA, Beijing 100853, China.
4
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing 400038, China.
5
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: happyzhou@vip.163.com.

Abstract

Transplantation of mesenchymal stem cells (MSCs) into the degenerated intervertebral disc (IVD) has shown promise for decelerating or arresting IVD degeneration. Cellular mechanical properties play crucial roles in regulating cell-matrix interactions, potentially reflecting specific changes that occur based on cellular phenotype and behavior. However, the effect of co-culturing of MSCs with nucleus pulposus cells (NPCs) on the mechanical properties of NPCs remains unknown. In our study, we demonstrated that co-culture of degenerated NPCs with MSCs resulted in significantly decreased mechanical moduli (elastic modulus, relaxed modulus, and instantaneous modulus) and increased biological activity (proliferation and expression of matrix genes) in degenerated NPCs, but not normal NPCs. SDF-1, CXCR4 ligand, was highly expressed in MSCs when co-cultured with degenerated NPCs. Inhibition of SDF-1 using CXCR4 antagonist AMD3100 or knocking-down CXCR4 in degenerated NPCs abolished the MSCs-induced decrease in the mechanical moduli and increased biological activity of degenerated NPCs, suggesting a crucial role for SDF-1/CXCR4 signaling. AKT and FAK inhibition attenuated the MSCs- or SDF-1-induced decrease in the mechanical moduli of degenerated NPCs. In conclusion, it was demonstrated in vitro that MSCs regulate the mechanical properties of degenerated NPCs through SDF-1/CXCR4/AKT signaling. These findings highlight a possible mechanical mechanism for MSCs-induced modulation with degenerated NPCs, which may be applicable to MSCs-based therapy for disc degeneration.

KEYWORDS:

AKT; Cellular mechanical properties; Intervertebral disc degeneration; Mesenchymal stem cell; Nucleus pulposus cell; SDF-1/CXCR4

PMID:
27163878
DOI:
10.1016/j.bbamcr.2016.05.004
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center