title: Impaired extracellular matrix structure resulting from malnutrition in ovariectomized mature rats.
abstract: Bone loss is a symptom related to disease and age, which reflects on bone cells and ECM. Discrepant regulation affects cell proliferation and ECM localization. Rat model of osteoporosis (OVX) was investigated against control rats (Sham) at young and old ages. Biophysical, histological and molecular techniques were implemented to examine the underlying cellular and extracellular matrix changes and to assess the mechanisms contributing to bone loss in the context of aging and the widely used osteoporotic models in rats. Bone loss exhibited a compromised function of bone cells and infiltration of adipocytes into bone marrow. However, the expression of genes regulating collagen catabolic process and adipogenesis was chronologically shifted in diseased bone in comparison with aged bone. The data showed the involvement of Wnt signaling inhibition in adipogenesis and bone loss due to over-expression of SOST in both diseased and aged bone. Further, in the OVX animals, an integrin-mediated ERK activation indicated the role of MAPK in osteoblastogenesis and adipogenesis. The increased PTH levels due to calcium and estrogen deficiency activated osteoblastogenesis. Thusly, RANKL-mediated osteoclastogenesis was initiated. Interestingly, the data show the role of MEPE regulating osteoclast-mediated resorption at late stages in osteoporotic bone. The interplay between ECM and bone cells change tissue microstructure and properties. The involvement of Wnt and MAPK pathways in activating cell proliferation has intriguing similarities to oncogenesis and myeloma. The study indicates the importance of targeting both pathways simultaneously to remedy metabolic bone diseases and age-related bone loss.
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig University, Giessen, Germany. thaqif.elkhassawna@chiru.med.uni-giessen.de.
authors.forename: Thaqif
authors.initials: T
authors.lastname: El Khassawna
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig University, Giessen, Germany. Wolfgang.boecker@chiru.med.uni-giessen.de.|Department of Trauma Surgery, University Hospital of Giessen-Marburg, Rudolf-Buchheim-Strasse 7, 35385, Giessen, Germany. Wolfgang.boecker@chiru.med.uni-giessen.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Böcker
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig University, Giessen, Germany. Katharina.brodsky@med.uni-giessen.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Brodsky
authors.affiliation: Department of Trauma Surgery, University Hospital of Giessen-Marburg, Rudolf-Buchheim-Strasse 7, 35385, Giessen, Germany. David.weisweiler@med.uni-giessen.de.
authors.forename: David
authors.initials: D
authors.lastname: Weisweiler
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig University, Giessen, Germany. Parameswari.govindarajan@chiru.med.uni-giessen.de.
authors.forename: Parameswari
authors.initials: P
authors.lastname: Govindarajan
authors.affiliation: Department of Radiology, University Hospital of Giessen-Marburg, Giessen, Germany. Marian.kampschulte@radiol.med.uni-giessen.de.
authors.forename: Marian
authors.initials: M
authors.lastname: Kampschulte
authors.affiliation: Department of Trauma Surgery, University Hospital of Giessen-Marburg, Rudolf-Buchheim-Strasse 7, 35385, Giessen, Germany. Ulrich.thormann@chiru.med.uni-giessen.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Thormann
authors.affiliation: Institute for Physical Chemistry, Justus-Liebig-University of Giessen, Giessen, Germany. Anja.henss@phys.chemie.uni-giessen.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Henss
authors.affiliation: Institute for Physical Chemistry, Justus-Liebig-University of Giessen, Giessen, Germany. Marcus.rohnke@phys.chemie.uni-giessen.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Rohnke
authors.affiliation: Department of Veterinary Clinical Sciences, Clinical Pathology and Clinical Pathophysiology, Justus-Liebig University Giessen, Giessen, Germany. Natali.bauer@vetmed.uni-giessen.de.
authors.forename: Natali
authors.initials: N
authors.lastname: Bauer
authors.affiliation: Center for Information Services and High Performance Computing, TU Dresden, Dresden, Germany. Robert.mueller@tu-dresden.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Müller
authors.affiliation: Center for Information Services and High Performance Computing, TU Dresden, Dresden, Germany. Andreas.deutsch@tu-dresden.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Deutsch
authors.affiliation: Institute of Orthopedic Research and Biomechanics, Centre of Musculoskeletal Research, University of Ulm, Ulm, Germany. Anita.ignatius@uni-ulm.de.
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
authors.affiliation: Institute of Orthopedic Research and Biomechanics, Centre of Musculoskeletal Research, University of Ulm, Ulm, Germany. Lutz.duerselen@uni-ulm.de.
authors.forename: Lutz
authors.initials: L
authors.lastname: Dürselen
authors.affiliation: Department of Diagnostic and Interventional Radiology, BG Trauma Hospital Frankfurt/Main, Frankfurt, Germany. Alexander.langheinrich@radiol.med.uni-giessen.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Langheinrich
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig University, Giessen, Germany. Katrin.S.lips@chiru.med.uni-giessen.de.
authors.forename: Katrin S
authors.initials: KS
authors.lastname: Lips
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig University, Giessen, Germany. Reinhard.schnettler@chiru.med.uni-giessen.de.|Department of Trauma Surgery, University Hospital of Giessen-Marburg, Rudolf-Buchheim-Strasse 7, 35385, Giessen, Germany. Reinhard.schnettler@chiru.med.uni-giessen.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schnettler
authors.affiliation: Laboratory of Experimental Trauma Surgery, Justus-Liebig University, Giessen, Germany. christian.heiss@chiru.med.uni-giessen.de.|Department of Trauma Surgery, University Hospital of Giessen-Marburg, Rudolf-Buchheim-Strasse 7, 35385, Giessen, Germany. christian.heiss@chiru.med.uni-giessen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D003094:Collagen; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D016023:Integrins / Q000378:metabolism; D044342:Malnutrition / Q000378:metabolism / Q000473:pathology*; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019485:Bone Morphogenetic Proteins; D016326:Extracellular Matrix Proteins; D005819:Genetic Markers; D016023:Integrins; C486031:Sost protein, rat; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Extracellular matrix; Malnutrition; Modeling; Osteocytes; Osteoporosis; Rat model; ToF-SIMS