Impaired extracellular matrix structure resulting from malnutrition in ovariectomized mature rats
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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.
KeywordsOsteoporosis Rat model Malnutrition Extracellular matrix ToF-SIMS Modeling Osteocytes
This study was supported by the Deutsche Forschungsgemeinschaft (DFG) within the SFB/Transregio 79. The authors would like to thank Annette Stengel and Gunhild Martels at Justus-Liebig University of Giessen for their technical assistance.
Compliance with ethical standards
Conflict of interest
Thaqif El Khassawna, Wolfgang Boecker, Katharina Brodsky, David Weisweiler, Parameswari Govindarajan, Marian Kampschulte, Katrin S. Lips, Ulrich Thormann, Marcus Rohnke, Anja Henss, Robert Mueller, Andreas Deutsch, Lutz Duerselen, Anita Ignatius, Alexander Langheinrich, Reinhard Schnettler and Christian Heiss declare that they have no conflict of interest.
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