title: Early changes in morphology, bone mineral density and matrix composition of vertebrae lead to disc degeneration in aged collagen IX -/- mice.
abstract: Collagen IX (Col IX) is an important component of the cartilage extracellularmatrix and has been associated with degenerative cartilage disorders and chondrodysplasias in humans. Further, polymorphisms in Col IX are known risk factors for the development of early intervertebral disc (IVD) degeneration. To understand the role of Col IX in the pathogenesis of IVD disorders, the spine of newborn and older Col IX deficient mice was systematically analyzed and compared to C57BL/6N controls. Morphology and bone parameters of the spine from newborn, 6 and 10 months old animals were investigated using μCT measurements. Histological staining was used to evaluate tissue structure and degree of degeneration. Localization and expression of extracellularmatrix proteins was analyzed in depth by immunofluorescence staining, immunoblotting, RT-PCR and in situ hybridization. High resolution imaging and stiffness measurements were performed by atomic force microscopy (AFM). Vertebral bodies of newborn Col IX-deficient mice were smaller and showed an increased mineral density compared to wild type animals. At birth, lack of Col IX led to a disrupted cellular organization in the cartilaginous endplate and a smaller nucleus pulposus of the IVD.Expression levels and localization of other extracellularmatrix proteins were strongly altered accompanied by a softening of cartilaginous tissues. In older animals, absence of Col IX caused earlier and more pronounced disc degeneration with annular fissures. The absence of Col IX induces early developmental, structural and biomechanical alterations in both vertebral body and intervertebral disc which eventually cause severe degenerative changes in the aging spine.
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, D-50931 Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kamper
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, D-50931 Cologne, Germany; Institute of Biomechanics and Orthopaedics, German Sport University Cologne, Cologne, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Hamann
authors.affiliation: Department of Applied Sciences and Mechatronics, Munich University of Applied Sciences, Lothstr. 34, 80335 Munich, Germany; Center for Applied Tissue Engineering and Regenerative Medicine, Munich University of Applied Sciences, Lothstr. 34, 80335 Munich, Germany; Center for NanoScience, Ludwig-Maximilians-Universität München, Geschwister-Scholl-Platz 1, 80539 Munich, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Prein
authors.affiliation: Department of Applied Sciences and Mechatronics, Munich University of Applied Sciences, Lothstr. 34, 80335 Munich, Germany; Center for Applied Tissue Engineering and Regenerative Medicine, Munich University of Applied Sciences, Lothstr. 34, 80335 Munich, Germany; Center for NanoScience, Ludwig-Maximilians-Universität München, Geschwister-Scholl-Platz 1, 80539 Munich, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Clausen-Schaumann
authors.affiliation: Laboratory of Experimental Surgery and Regenerative Medicine, Department of General, Trauma, Hand and Plastic Surgery, Clinical Center University of Munich, Nussbaumstr. 20, 80336 Munich, Germany.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Farkas
authors.affiliation: Center for Applied Tissue Engineering and Regenerative Medicine, Munich University of Applied Sciences, Lothstr. 34, 80335 Munich, Germany; Laboratory of Experimental Surgery and Regenerative Medicine, Department of General, Trauma, Hand and Plastic Surgery, Clinical Center University of Munich, Nussbaumstr. 20, 80336 Munich, Germany.
authors.forename: Attila
authors.initials: A
authors.lastname: Aszodi
authors.affiliation: Cologne Center for Musculoskeletal Biomechanics (CCMB), University of Cologne, D-50931 Cologne, Germany; Institute of Biomechanics and Orthopaedics, German Sport University Cologne, Cologne, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Niehoff
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, D-50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, D-50931 Cologne, Germany; Cologne Center for Musculoskeletal Biomechanics (CCMB), University of Cologne, D-50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, D-50931 Cologne, Germany.
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, D-50931 Cologne, Germany; Cologne Center for Musculoskeletal Biomechanics (CCMB), University of Cologne, D-50931 Cologne, Germany. Electronic address: frank.zaucke@uni-koeln.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Zaucke
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015519:Bone Density; D024081:Collagen Type IX / Q000172:deficiency*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013131:Spine / Q000473:pathology*
chemical_list: D024081:Collagen Type IX; D016326:Extracellular Matrix Proteins