Browsing by Author "Séguin, Cheryle A."

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    Impaired Annulus Fibrosis Development and Vertebral Fusion Cause Severe Scoliosis in Mice with Deficiency of JNK1 and JNK2
    (Elsevier, 2019) Ulici, Veronica; Kelley, Kathryn L.; Longobardi, Lara; McNulty, Margaret A.; Livingston, Eric W.; Bateman, Ted A.; Séguin, Cheryle A.; Louer, Craig R.; Loeser, Richard F.; Anatomy and Cell Biology, IU School of Medicine
    MAP kinases, including JNK, play an important role in the development and function of a large variety of tissues. We analyzed the skeletal phenotype of JNK1 and JNK2 double knockout (dKO) mice (JNK1fl/flCol2-Cre/JNK2-/-) and control genotypes, including single knockouts, at different embryonic and postnatal stages. The JNK1/2 dKO mice displayed a severe scoliotic phenotype that began during development and was grossly apparent around weaning age. Alcian blue staining of embryos (E17.5) showed abnormal fusion of the posterior spinal elements. In the adult mice, fusion of vertebral bodies and of spinous and transverse processes was noted by microCT, Alcian blue/Alizarin red stain and histology. The long bones developed normally and histological sections of the growth plate and articular cartilage did not reveal significant abnormalities. Histological sections of the vertebral column at E15.5 and E17.5 revealed an abnormal organization of the annulus fibrosus in the dKOs, with chondrocyte-like cells and fusion of dorsal processes. Spinal sections in 10-week–old dKO mice showed replacement of intervertebral disc structures (annulus fibrosus and nucleus pulposus) by cartilage and bone tissues, with cells staining for markers of hypertrophic chondrocytes including collagen X and Runx2. These findings demonstrate a requirement for both JNK1 and JNK2 in the normal development of the axial skeleton with loss of JNK signaling resulting in abnormal endochondral bone formation and subsequent severe scoliosis.
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    Impaired Annulus Fibrosus Development and Vertebral Fusion Cause Severe Scoliosis in Mice with Deficiency of c-Jun NH2-Terminal Kinases 1 and 2
    (Elsevier, 2019-04) Ulici, Veronica; Kelley, Kathryn L.; Longobardi, Lara; McNulty, Margaret A.; Livingston, Eric W.; Bateman, Ted A.; Séguin, Cheryle A.; Louer, Craig R.; Loeser, Richard F.; Anatomy and Cell Biology, School of Medicine
    Mitogen-activated protein kinases, including c-Jun NH2-terminal kinase (JNK), play an important role in the development and function of a large variety of tissues. The skeletal phenotype of JNK1 and JNK2 double-knockout (dKO) mice (JNK1fl/flCol2-Cre/JNK2−/−) and control genotypes were analyzed at different embryonic and postnatal stages. JNK1/2 dKO mice displayed a severe scoliotic phenotype beginning during development that was grossly apparent around weaning age. Alcian blue staining at embryonic day 17.5 showed abnormal fusion of the posterior spinal elements. In adult mice, fusion of vertebral bodies and of spinous and transverse processes was noted by micro–computed tomography, Alcian blue/Alizarin red staining, and histology. The long bones developed normally, and histologic sections of growth plate and articular cartilage revealed no significant abnormalities. Histologic sections of the vertebral column at embryonic days 15.5 and 17.5 revealed an abnormal organization of the annulus fibrosus in the dKOs, with chondrocyte-like cells and fusion of dorsal processes. Spinal sections in 10-week–old dKO mice showed replacement of intervertebral disk structures (annulus fibrosus and nucleus pulposus) by cartilage and bone tissues, with cells staining for markers of hypertrophic chondrocytes, including collagen X and runt-related transcription factor 2. These findings demonstrate a requirement for both JNK1 and JNK2 in the normal development of the axial skeleton. Loss of JNK signaling results in abnormal endochondral bone formation and subsequent severe scoliosis.
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    Severe osteoarthritis in aged PANX3 knockout mice: implications for a novel primary osteoarthritis model
    (Oxford University Press, 2025-04-07) Wakefield, Brent; Tang, Justin; Balanta-Melo, Julián; Hutchinson, Jeffrey L.; Kanji, Rehanna; Herold, Geneva; O’Donnell, Brooke L.; Brooks, Courtney; Kiser, Patti; Grol, Matthew W.; Séguin, Cheryle A.; Plotkin, Lilian I.; Beier, Frank; Penuela, Silvia; Anatomy, Cell Biology and Physiology, School of Medicine
    Osteoarthritis (OA) is a multifactorial disease associated with aging. As the molecular mechanisms underpinning the pathogenesis of this disease are unclear, there are no disease-modifying drugs to combat OA. Pannexin 3 (PANX3) has been shown to promote cartilage loss during posttraumatic OA. In contrast, the ablation of Panx3in male mice results in spontaneous full-thickness cartilage lesions at 24 mo of age. While protected from traumatic intervertebral disc (IVD) degeneration, Panx3KO mice show signs of IVD disease with altered disc mechanics. Whether the deleterious effects of ablating Panx3in aging are the result of accumulated mechanical damage is unknown. We used male and female WT and global Panx3KO C57Bl6 mice aged 18 mo of age. Mice were then randomized to sedentary (SED) or forced treadmill running (FEX) for 6 wk. Knee joint tissues, including the patellar tendon, quadriceps and distal patellar enthesis, and synovium were analyzed histologically and through micro-CT, along with lumbar spine IVDs. Half of male and female SED Panx3KO mice developed full-thickness cartilage lesions, severe synovitis, and ectopic fibrocartilage deposition and calcification of the knee joints in comparison to all other conditions. Panx3KO mice with severe OA show signs of quadriceps and patellar enthesitis, characterized by bone and marrow formation. Forced treadmill running did not seem to exacerbate these phenotypes in male or female Panx3KO mice; however, it may have contributed to the development of lateral compartment OA. The IVDs of aged Panx3KO mice displayed no apparent differences to control mice, and forced treadmill running had no further effects in either genotype. We conclude that aged Panx3KO mice show features of late-stage primary OA, including full-thickness cartilage erosion, severe synovitis, and enthesitis. These data suggest that the deletion of Panx3is deleterious to synovial joint health in aging.