Ion elemental-optimized layered double hydroxide nanoparticles promote chondrogenic differentiation and intervertebral disc regeneration of mesenchymal stem cells through focal adhesion signaling pathway

Chronic low back pain and dyskinesia caused by intervertebral disc degeneration (IDD) are seriously aggravated and become more prevalent with age. Current clinical treatments do not restore the biological structure and inherent function of the disc. The emergence of tissue engineering and regenerati...

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Published inBioactive materials Vol. 22; pp. 75 - 90
Main Authors Wang, Zhaojie, Yang, Huiyi, Xu, Xu, Hu, Hongxing, Bai, Yuxin, Hai, Jian, Cheng, Liming, Zhu, Rongrong
Format Journal Article
LanguageEnglish
Published Elsevier B.V 01.04.2023
KeAi Publishing
KeAi Communications Co., Ltd
Subjects
Chondrogenic differentiation
Focal adhesion signaling pathway
Intervertebral disc degeneration
Layered double hydroxide
Mesenchymal stem cells
Intervertebral disc degeneration
Chondrogenic differentiation
Layered double hydroxide
Focal adhesion signaling pathway
Mesenchymal stem cells
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Abstract Chronic low back pain and dyskinesia caused by intervertebral disc degeneration (IDD) are seriously aggravated and become more prevalent with age. Current clinical treatments do not restore the biological structure and inherent function of the disc. The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD. We synthesized biocompatible layered double hydroxide (LDH) nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining, qPCR, and immunofluorescence analyses. LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model. Repair and regeneration evaluated using X-ray, magnetic resonance imaging, and tissue immunostaining 4–12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure. Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix (ECM) and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration. The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment. [Display omitted] •LDH nanoparticles with different elemental compositions are constructed to optimize the chondrogenic differentiation of hUC-MSCs.•Optimized-LDH pretreated hUC-MSCs transplantation show recovery of disc space height and integrated tissue structure.•ECM and focal adhesion signaling pathway play significant roles in LDH-promoted cell differentiation and tissue regeneration.•Ion-specific optimizing LDH provides theoretical basis for clinical transformation on IDD treatment.
AbstractList Chronic low back pain and dyskinesia caused by intervertebral disc degeneration (IDD) are seriously aggravated and become more prevalent with age. Current clinical treatments do not restore the biological structure and inherent function of the disc. The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD. We synthesized biocompatible layered double hydroxide (LDH) nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining, qPCR, and immunofluorescence analyses. LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model. Repair and regeneration evaluated using X-ray, magnetic resonance imaging, and tissue immunostaining 4–12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure. Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix (ECM) and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration. The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment.
Chronic low back pain and dyskinesia caused by intervertebral disc degeneration (IDD) are seriously aggravated and become more prevalent with age. Current clinical treatments do not restore the biological structure and inherent function of the disc. The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD. We synthesized biocompatible layered double hydroxide (LDH) nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining, qPCR, and immunofluorescence analyses. LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model. Repair and regeneration evaluated using X-ray, magnetic resonance imaging, and tissue immunostaining 4–12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure. Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix (ECM) and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration. The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment. [Display omitted] •LDH nanoparticles with different elemental compositions are constructed to optimize the chondrogenic differentiation of hUC-MSCs.•Optimized-LDH pretreated hUC-MSCs transplantation show recovery of disc space height and integrated tissue structure.•ECM and focal adhesion signaling pathway play significant roles in LDH-promoted cell differentiation and tissue regeneration.•Ion-specific optimizing LDH provides theoretical basis for clinical transformation on IDD treatment.
Chronic low back pain and dyskinesia caused by intervertebral disc degeneration (IDD) are seriously aggravated and become more prevalent with age. Current clinical treatments do not restore the biological structure and inherent function of the disc. The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD. We synthesized biocompatible layered double hydroxide (LDH) nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining, qPCR, and immunofluorescence analyses. LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model. Repair and regeneration evaluated using X-ray, magnetic resonance imaging, and tissue immunostaining 4–12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure. Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix (ECM) and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration. The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment. Image 1 • LDH nanoparticles with different elemental compositions are constructed to optimize the chondrogenic differentiation of hUC-MSCs. • Optimized-LDH pretreated hUC-MSCs transplantation show recovery of disc space height and integrated tissue structure. • ECM and focal adhesion signaling pathway play significant roles in LDH-promoted cell differentiation and tissue regeneration. • Ion-specific optimizing LDH provides theoretical basis for clinical transformation on IDD treatment.
Author Bai, Yuxin
Xu, Xu
Hu, Hongxing
Cheng, Liming
Yang, Huiyi
Wang, Zhaojie
Hai, Jian
Zhu, Rongrong
Author_xml – sequence: 1
  givenname: Zhaojie
  surname: Wang
  fullname: Wang, Zhaojie
  organization: Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai, 200065, China
– sequence: 2
  givenname: Huiyi
  surname: Yang
  fullname: Yang, Huiyi
  organization: Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai, 200065, China
– sequence: 3
  givenname: Xu
  surname: Xu
  fullname: Xu, Xu
  organization: Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai, 200065, China
– sequence: 4
  givenname: Hongxing
  surname: Hu
  fullname: Hu, Hongxing
  organization: Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai, 200065, China
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  givenname: Yuxin
  surname: Bai
  fullname: Bai, Yuxin
  organization: Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai, 200065, China
– sequence: 6
  givenname: Jian
  surname: Hai
  fullname: Hai, Jian
  organization: Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai, 200065, China
– sequence: 7
  givenname: Liming
  surname: Cheng
  fullname: Cheng, Liming
  email: limingcheng@tongji.edu.cn
  organization: Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai, 200065, China
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  givenname: Rongrong
  orcidid: 0000-0002-3955-5965
  surname: Zhu
  fullname: Zhu, Rongrong
  email: rrzhu@tongji.edu.cn
  organization: Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai, 200065, China
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Keywords Intervertebral disc degeneration
Chondrogenic differentiation
Layered double hydroxide
Focal adhesion signaling pathway
Mesenchymal stem cells
Language English
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Snippet Chronic low back pain and dyskinesia caused by intervertebral disc degeneration (IDD) are seriously aggravated and become more prevalent with age. Current...
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SubjectTerms Chondrogenic differentiation
Focal adhesion signaling pathway
Intervertebral disc degeneration
Layered double hydroxide
Mesenchymal stem cells
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Title Ion elemental-optimized layered double hydroxide nanoparticles promote chondrogenic differentiation and intervertebral disc regeneration of mesenchymal stem cells through focal adhesion signaling pathway
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