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Full-Text Articles in Orthopedics
A New Perspective On Intervertebral Disc Calcification-From Bench To Bedside, Emanuel Novais, Rajkishen Narayanan, Jose Canseco, Koen Van De Wetering, Christopher Kepler, Alan Hilibrand, Alex Vaccaro, Makarand Risbud
A New Perspective On Intervertebral Disc Calcification-From Bench To Bedside, Emanuel Novais, Rajkishen Narayanan, Jose Canseco, Koen Van De Wetering, Christopher Kepler, Alan Hilibrand, Alex Vaccaro, Makarand Risbud
Department of Orthopaedic Surgery Faculty Papers
Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular …
Editorial: Intervertebral Disc Degeneration And Osteoarthritis: Mechanisms Of Disease And Functional Repair., Graciosa Q Teixeira, Jana Riegger, Raquel M Gonçalves, Makarand V. Risbud
Editorial: Intervertebral Disc Degeneration And Osteoarthritis: Mechanisms Of Disease And Functional Repair., Graciosa Q Teixeira, Jana Riegger, Raquel M Gonçalves, Makarand V. Risbud
Department of Orthopaedic Surgery Faculty Papers
No abstract provided.
Long-Term Treatment With Senolytic Drugs Dasatinib And Quercetin Ameliorates Age-Dependent Intervertebral Disc Degeneration In Mice, Emanuel J Novais, Victoria Tran, Shira N Johnston, Kayla R Darris, Alex J Roupas, Garrett A Sessions, Irving Shapiro, Brian O Diekman, Makarand V Risbud
Long-Term Treatment With Senolytic Drugs Dasatinib And Quercetin Ameliorates Age-Dependent Intervertebral Disc Degeneration In Mice, Emanuel J Novais, Victoria Tran, Shira N Johnston, Kayla R Darris, Alex J Roupas, Garrett A Sessions, Irving Shapiro, Brian O Diekman, Makarand V Risbud
Department of Orthopaedic Surgery Faculty Papers
Intervertebral disc degeneration is highly prevalent within the elderly population and is a leading cause of chronic back pain and disability. Due to the link between disc degeneration and senescence, we explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice. We treated C57BL/6 mice beginning at 6, 14, and 18 months of age, and analyzed them at 23 months of age. Interestingly, 6- and 14-month D + Q cohorts show lower incidences of degeneration, and the treatment results in a significant decrease in senescence markers p16INK4a, …
Tnf-Α Promotes Nuclear Enrichment Of The Transcription Factor Tonebp/Nfat5 To Selectively Control Inflammatory But Not Osmoregulatory Responses In Nucleus Pulposus Cells., Zariel I. Johnson, Alexandra C. Doolittle, Joseph W. Snuggs, Irving M. Shapiro, Christine L. Le Maitre, Makarand V. Risbud
Tnf-Α Promotes Nuclear Enrichment Of The Transcription Factor Tonebp/Nfat5 To Selectively Control Inflammatory But Not Osmoregulatory Responses In Nucleus Pulposus Cells., Zariel I. Johnson, Alexandra C. Doolittle, Joseph W. Snuggs, Irving M. Shapiro, Christine L. Le Maitre, Makarand V. Risbud
Department of Orthopaedic Surgery Faculty Papers
Intervertebral disc degeneration (IDD) causes chronic back pain and is linked to production of proinflammatory molecules by nucleus pulposus (NP) and other disc cells. Activation of tonicity-responsive enhancer-binding protein (TonEBP)/NFAT5 by non-osmotic stimuli, including proinflammatory molecules, occurs in cells involved in immune response. However, whether inflammatory stimuli activate TonEBP in NP cells and whether TonEBP controls inflammation during IDD is unknown. We show that TNF-α, but not IL-1β or LPS, promoted nuclear enrichment of TonEBP protein. However, TNF-α-mediated activation of TonEBP did not cause induction of osmoregulatory genes. RNA sequencing showed that 8.5% of TNF-α transcriptional responses were TonEBP-dependent and …
Rna Sequencing Reveals A Role Of Tonebp Transcription Factor In Regulation Of Pro-Inflammatory Genes In Response To Hyperosmolarity In Healthy Nucleus Pulposus Cells: A Homeostatic Response?, Zariel I. Johnson, Irving M. Shapiro, Makarand V. Risbud
Rna Sequencing Reveals A Role Of Tonebp Transcription Factor In Regulation Of Pro-Inflammatory Genes In Response To Hyperosmolarity In Healthy Nucleus Pulposus Cells: A Homeostatic Response?, Zariel I. Johnson, Irving M. Shapiro, Makarand V. Risbud
Department of Orthopaedic Surgery Faculty Papers
Transcription factor tonicity-responsive enhancer-binding protein (TonEBP/NFAT5) is critical for osmo-adaptation and extracellular matrix homeostasis of nucleus pulposus (NP) cells in their hypertonic tissue niche. Recent studies implicate TonEBP signaling in inflammatory disease and rheumatoid arthritis pathogenesis. However, broader functions of TonEBP in the disc remain unknown. RNA sequencing was performed on NP cells with TonEBP knockdown under hypertonic conditions. 1140 TonEBP-dependent genes were identified and categorized using Ingenuity Pathway Analysis. Bioinformatic analysis showed enrichment of matrix homeostasis and cytokine/chemokine signaling pathways. C-C motif chemokine ligand 2 (CCL2), interleukin 6 (IL6), tumor necrosis factor (TNF), and nitric oxide synthase 2 (NOS2) …