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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 Jun 2022

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, …


Abcc6 Null Mice-A Model For Mineralization Disorder Pxe Shows Vertebral Osteopenia Without Enhanced Intervertebral Disc Calcification With Aging, Paige K Boneski, Vedavathi Madhu, Ryan Tomlinson, Irving Shapiro, Koen Van De Wetering, Makarand V Risbud Feb 2022

Abcc6 Null Mice-A Model For Mineralization Disorder Pxe Shows Vertebral Osteopenia Without Enhanced Intervertebral Disc Calcification With Aging, Paige K Boneski, Vedavathi Madhu, Ryan Tomlinson, Irving Shapiro, Koen Van De Wetering, Makarand V Risbud

Department of Orthopaedic Surgery Faculty Papers

Chronic low back pain is a highly prevalent health condition intricately linked to intervertebral disc degeneration. One of the prominent features of disc degeneration that is commonly observed with aging is dystrophic calcification. ATP-binding cassette sub-family C member 6 (ABCC6), a presumed ATP efflux transporter, is a key regulator of systemic levels of the mineralization inhibitor pyrophosphate (PPi). Mutations in ABCC6 result in pseudoxanthoma elasticum (PXE), a progressive human metabolic disorder characterized by mineralization of the skin and elastic tissues. The implications of ABCC6 loss-of-function on pathological mineralization of structures in the spine, however, are unknown. Using the Abcc6 -/- …


Enhancing Precision In Bioprinting Utilizing Fuzzy Systems, Ashkan Sedigh, Dayna Dipiero, Kristy M. Shine, Ryan E. Tomlinson Jan 2022

Enhancing Precision In Bioprinting Utilizing Fuzzy Systems, Ashkan Sedigh, Dayna Dipiero, Kristy M. Shine, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Bioprinting facilitates the generation of complex, three-dimensional (3D), cell-based constructs for a variety of applications. Although multiple bioprinting technologies have been developed, extrusion-based systems have become the dominant technology due to the diversity of substrate materials (i.e. bioinks) that can be accommodated, either individually or in combination. Each bioink has unique material properties and extrusion characteristics that limit bioprinting precision, particularly when generating identically shaped constructs from different bioinks. Here, we aimed to achieve high precision (i.e. repeatability) across samples by generating bioink-specific printing parameters using a systematic approach. We hypothesized that a Fuzzy system could be used as a …