title: Mesenchymal stem cells regulate mechanical properties of human degenerated nucleus pulposus cells through SDF-1/CXCR4/AKT axis.
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.
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Ming-Han
authors.initials: MH
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Bai-Shi-Jiao
authors.initials: BS
authors.lastname: Bian
authors.affiliation: Department of Orthopedics, General Hospital of Chinese PLA, Beijing 100853, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Lan-Tao
authors.initials: LT
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Cui
authors.affiliation: 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.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: happyzhou@vip.163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D053674:Aggrecans / Q000096:biosynthesis / Q000235:genetics; D001596:Benzylamines; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018920:Coculture Techniques; D024043:Collagen Type II / Q000096:biosynthesis / Q000235:genetics; D000080027:Cyclams; D055119:Elastic Modulus; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D055959:Intervertebral Disc Degeneration / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D018625:Microscopy, Atomic Force; D000070614:Nucleus Pulposus / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D001596:Benzylamines; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D024043:Collagen Type II; D000080027:Cyclams; D006571:Heterocyclic Compounds; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C088327:plerixafor
keywords: AKT; Cellular mechanical properties; Intervertebral disc degeneration; Mesenchymal stem cell; Nucleus pulposus cell; SDF-1/CXCR4