Matthew A Veras1, Matthew R McCann1,2, Neil A Tenn1, Cheryle A Séguin1. 1. Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The Bone and Joint Institute, The University of Western Ontario, London, Canada. 2. Sydney Medical School, University of Sydney, Sydney, Australia.
Abstract
Purpose/Aim: The intervertebral disc (IVD) is composed of cell types whose subtle phenotypic differences allow for the formation of distinct tissues. The role of the nucleus pulposus (NP) in the initiation and progression of IVD degeneration is well established; however, the genes and pathways associated with NP degeneration are poorly characterized.Materials and Methods: Using a genetic strategy for IVD lineage-specific fluorescent reporter expression to isolate cells, gene expression and bioinformatic analysis was conducted on the murine NP at 2.5, 6, and 21 months-of-age and the annulus fibrosus (AF) at 2.5 and 6 months-of-age. A subset of differentially regulated genes was validated by qRT-PCR. Results: Transcriptome analysis identified distinct profiles of NP and AF gene expression that were remarkably consistent at 2.5 and 6 months-of-age. Prg4, Cilp, Ibsp and Comp were increased >50-fold in the AF relative to NP. The most highly enriched NP genes included Dsc3 and Cdh6, members of the cadherin superfamily, and microRNAs mir218-1 and mir490. Changes in the NP between 2.5 and 6 months-of-age were associated with up-regulation of molecular functions linked to laminin and Bmp receptor binding (including up-regulation of Bmp5 & 7), with the most up-regulated genes being Mir703, Shh, and Sfrp5. NP degeneration was associated with molecular functions linked to alpha-actinin binding (including up-regulation of Ttn & Myot) and cytoskeletal protein binding, with the overall most up-regulated genes being Rnu3a, Snora2b and Mir669h.Conclusions: This study provided insight into the phenotypes of NP and AF cells, and identified candidate pathways that may regulate degeneration.
Purpose/Aim: The intervertebral disc (IVD) is composed of cell types whose subtle phenotypic differences allow for the formation of distinct tissues. The role of the nucleus pulposus (NP) in the initiation and progression of IVD degeneration is well established; however, the genes and pathways associated with NP degeneration are poorly characterized.Materials and Methods: Using a genetic strategy for IVD lineage-specific fluorescent reporter expression to isolate cells, gene expression and bioinformatic analysis was conducted on the murine NP at 2.5, 6, and 21 months-of-age and the annulus fibrosus (AF) at 2.5 and 6 months-of-age. A subset of differentially regulated genes was validated by qRT-PCR. Results: Transcriptome analysis identified distinct profiles of NP and AF gene expression that were remarkably consistent at 2.5 and 6 months-of-age. Prg4, Cilp, Ibsp and Comp were increased >50-fold in the AF relative to NP. The most highly enriched NP genes included Dsc3 and Cdh6, members of the cadherin superfamily, and microRNAs mir218-1 and mir490. Changes in the NP between 2.5 and 6 months-of-age were associated with up-regulation of molecular functions linked to laminin and Bmp receptor binding (including up-regulation of Bmp5 & 7), with the most up-regulated genes being Mir703, Shh, and Sfrp5. NP degeneration was associated with molecular functions linked to alpha-actinin binding (including up-regulation of Ttn & Myot) and cytoskeletal protein binding, with the overall most up-regulated genes being Rnu3a, Snora2b and Mir669h.Conclusions: This study provided insight into the phenotypes of NP and AF cells, and identified candidate pathways that may regulate degeneration.
Authors: Vivian Tam; Peikai Chen; Anita Yee; Nestor Solis; Theo Klein; Mateusz Kudelko; Rakesh Sharma; Wilson Cw Chan; Christopher M Overall; Lisbet Haglund; Pak C Sham; Kathryn Song Eng Cheah; Danny Chan Journal: Elife Date: 2020-12-31 Impact factor: 8.140
Authors: Mitchel C Whittal; Sarah J Poynter; Kayla Samms; K Josh Briar; Sabrina I Sinopoli; Magali Millecamps; Laura S Stone; Stephanie J DeWitte-Orr; Diane E Gregory Journal: Eur Spine J Date: 2022-07-11 Impact factor: 2.721
Authors: Lorenzo M Fernandes; Nazir M Khan; Camila M Trochez; Meixue Duan; Martha E Diaz-Hernandez; Steven M Presciutti; Greg Gibson; Hicham Drissi Journal: Sci Rep Date: 2020-09-17 Impact factor: 4.379
Authors: Mandy J Peffers; Tim J M Welting; Ellen G J Ripmeester; Marjolein M J Caron; G G H van den Akker; Don A M Surtel; Andy Cremers; Panagiotis Balaskas; Philip Dyer; Bas A C Housmans; Alzbeta Chabronova; Aibek Smagul; Yongxiang Fang; Lodewijk W van Rhijn Journal: Sci Rep Date: 2020-08-10 Impact factor: 4.379