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Expansion of FGFR3-positive nucleus pulposus cells plays important roles in postnatal nucleus pulposus growth and regeneration
Xu, Meng1,2; Huang, Junlan1; Jin, Min1; Jiang, Wanling1; Luo, Fengtao1; Tan, Qiaoyan1; Zhang, Ruobin1; Luo, Xiaoqing1; Kuang, Liang1; Zhang, Dali1; Liang, Sen1; Qi, Huabing1; Chen, Hangang1; Ni, Zhenhong1; Su, Nan1; Yang, Jing1; Du, Xiaolan1; Chen, Bo3; Deng, Chuxia4; Xie, Yangli1; Chen, Lin1
2022-06-03
Source PublicationStem Cell Research & Therapy
ISSN1757-6512
Volume13Pages:227
Abstract

Background: Intervertebral disc degeneration (IVDD) can cause low back pain, a major public health concern. IVDD is characterized with loss of cells especially those in nucleus pulposus (NP), due to the limited proliferative potential and regenerative ability. Few studies, however, have been carried out to investigate the in vivo proliferation events of NP cells and the cellular contribution of a specific subpopulation of NP during postnatal growth or regeneration. Methods: We generated FGFR3-3*Flag-IRES-GFP mice and crossed FGFR3-CreERT2 mice with Rosa26-mTmG, Rosa26-DTA and Rosa26-Confetti mice, respectively, to perform inducible genetic tracing studies. Results: Expression of FGFR3 was found in the outer region of NP with co-localized expressions of proliferating markers. By fate mapping studies, FGFR3-positive (FGFR3) NP cells were found proliferate from outer region to inner region of NP during postnatal growth. Clonal lineage tracing by Confetti mice and ablation of FGFR3 NP cells by DTA mice further revealed that the expansion of the FGFR3 cells was required for the morphogenesis and homeostasis of postnatal NP. Moreover, in degeneration and regeneration model of mouse intervertebral disc, FGFR3 NP cells underwent extensive expansion during the recovery stage. Conclusion: Our present work demonstrates that FGFR3 NP cells are novel subpopulation of postnatal NP with long-existing proliferative capacity shaping the adult NP structure and participating in the homeostasis maintenance and intrinsic repair of NP. These findings may facilitate the development of new therapeutic approaches for IVD regeneration.

KeywordIntervertebral Disc Degeneration Nucleus Pulposus Cell Proliferation Fgfr3 Genetic Mouse Models
DOI10.1186/s13287-022-02903-2
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaCell Biology ; Research & Experimental Medicine
WOS SubjectCell & Tissue Engineering ; Cell Biology ; Medicine, Research & Experimental
WOS IDWOS:000805834900010
PublisherBMC,CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Scopus ID2-s2.0-85131636881
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Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorXie, Yangli; Chen, Lin
Affiliation1.Laboratory of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, China
2.Department of Rehabilitation Medicine, General Hospital of Central Theater Command of Chinese People’s Liberation Army, Wuhan, China
3.Department of Spine Surgery, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China
4.Faculty of Health Sciences, University of Macau, Macao
Recommended Citation
GB/T 7714
Xu, Meng,Huang, Junlan,Jin, Min,et al. Expansion of FGFR3-positive nucleus pulposus cells plays important roles in postnatal nucleus pulposus growth and regeneration[J]. Stem Cell Research & Therapy, 2022, 13, 227.
APA Xu, Meng., Huang, Junlan., Jin, Min., Jiang, Wanling., Luo, Fengtao., Tan, Qiaoyan., Zhang, Ruobin., Luo, Xiaoqing., Kuang, Liang., Zhang, Dali., Liang, Sen., Qi, Huabing., Chen, Hangang., Ni, Zhenhong., Su, Nan., Yang, Jing., Du, Xiaolan., Chen, Bo., Deng, Chuxia., ...& Chen, Lin (2022). Expansion of FGFR3-positive nucleus pulposus cells plays important roles in postnatal nucleus pulposus growth and regeneration. Stem Cell Research & Therapy, 13, 227.
MLA Xu, Meng,et al."Expansion of FGFR3-positive nucleus pulposus cells plays important roles in postnatal nucleus pulposus growth and regeneration".Stem Cell Research & Therapy 13(2022):227.
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