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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 …
Loss Of Function Mutation In Ank Causes Aberrant Mineralization And Acquisition Of Osteoblast-Like-Phenotype By The Cells Of The Intervertebral Disc, Takashi Ohnishi, Victoria Tran, Kimheak Sao, Pranay Ramteke, William Querido, Ruteja A. Barve, Koen Van De Wetering, Makarand V. Risbud
Loss Of Function Mutation In Ank Causes Aberrant Mineralization And Acquisition Of Osteoblast-Like-Phenotype By The Cells Of The Intervertebral Disc, Takashi Ohnishi, Victoria Tran, Kimheak Sao, Pranay Ramteke, William Querido, Ruteja A. Barve, Koen Van De Wetering, Makarand V. Risbud
Department of Orthopaedic Surgery Faculty Papers
Pathological mineralization of intervertebral disc is debilitating and painful and linked to disc degeneration in a subset of human patients. An adenosine triphosphate efflux transporter, progressive ankylosis (ANK) is a regulator of extracellular inorganic pyrophosphate levels and plays an important role in tissue mineralization. However, the function of ANK in intervertebral disc has not been fully explored. Herein we analyzed the spinal phenotype of Ank mutant mice (ank/ank) with attenuated ANK function. Micro-computed tomography and histological analysis showed that loss of ANK function results in the aberrant annulus fibrosus mineralization and peripheral disc fusions with cranial to caudal progression in …
The Cgas-Sting Pathway Affects Vertebral Bone But Does Not Promote Intervertebral Disc Cell Senescence Or Degeneration, Olivia K. Ottone, C. James Kim, John A. Collins, Makarand V. Risbud
The Cgas-Sting Pathway Affects Vertebral Bone But Does Not Promote Intervertebral Disc Cell Senescence Or Degeneration, Olivia K. Ottone, C. James Kim, John A. Collins, Makarand V. Risbud
Department of Orthopaedic Surgery Faculty Papers
The DNA-sensing cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP) and mediates type-I interferon inflammatory responses to foreign viral and bacterial DNA as well as self-DNA. Studies of the intervertebral disc in humans and mice demonstrate associations between aging, increased cell senescence, and disc degeneration. Herein we assessed the role of STING in SASP promotion in STING gain- (N153S) and loss-of-function mouse models. N153S mice evidenced elevated circulating levels of proinflammatory markers including IL-1β, IL-6, and TNF-α, showed elevated monocyte and macrophage abundance in the vertebral marrow, and exhibited a mild trabecular and cortical bone phenotype in caudal vertebrae. Interestingly, …
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, …
Tonebp Regulates The Hyperosmotic Expression Of Aquaporin 1 And 5 In The Intervertebral Disc., Joseph Snuggs, Steven Tessier, R A B Bunning, Irving Shapiro, Makarand V Risbud, Christine Lyn Le Maitre
Tonebp Regulates The Hyperosmotic Expression Of Aquaporin 1 And 5 In The Intervertebral Disc., Joseph Snuggs, Steven Tessier, R A B Bunning, Irving Shapiro, Makarand V Risbud, Christine Lyn Le Maitre
Department of Orthopaedic Surgery Faculty Papers
The central region of the intervertebral disc (IVD) is rich in proteoglycans, leading to a hyperosmotic environment, which fluctuates with daily loading. The cells of the nucleus pulposus (NP cells) have adapted to this environment via the function of tonicity enhancer binding protein (TonEBP), and NP cells have been shown to express several water channels known as aquaporins (AQP). We have previously shown that AQP1 and 5 decrease during IVD degeneration. Here, the regulation of AQP1 and 5 by hyperosmotic conditions and the role of TonEBP in this regulation was investigated. AQP1 and 5 gene expression was upregulated by hyperosmotic …
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 …
New Horizons In Spine Research: Intervertebral Disc Repair And Regeneration., James C Iatridis, James Kang, Rita Kandel, Makarand V. Risbud
New Horizons In Spine Research: Intervertebral Disc Repair And Regeneration., James C Iatridis, James Kang, Rita Kandel, Makarand V. Risbud
Department of Orthopaedic Surgery Faculty Papers
No abstract provided.
Understanding Nucleus Pulposus Cell Phenotype: A Prerequisite For Stem Cell Based Therapies To Treat Intervertebral Disc Degeneration., Hyowon Choi, Zariel I. Johnson, Makarand V. Risbud
Understanding Nucleus Pulposus Cell Phenotype: A Prerequisite For Stem Cell Based Therapies To Treat Intervertebral Disc Degeneration., Hyowon Choi, Zariel I. Johnson, Makarand V. Risbud
Department of Orthopaedic Surgery Faculty Papers
Intervertebral disc (IVD) degeneration and associated low back pain (LBP) remains a major burden to our society without significant improvements in treatment strategies or patient's quality of life. While the recent cell-transplantation studies for treatment of degenerative disc disease have shown promising results, to better gauge the success and functional outcomes of these therapies, it is crucial to understand if transplanted cells give rise to healthy nucleus pulposus (NP) tissue. NP cell phenotype is unique and is defined by expression of a characteristic set of markers that reflect specialized physiology and function. This review summarizes phenotypic markers that mirror the …