Impaired extracellular matrix structure resulting from malnutrition in ovariectomized mature rats

作者：El Khassawna Thaqif; Boecker Wolfgang; Brodsky Katharina; Weisweiler David; Govindarajan Parameswari; Kampschulte Marian; Thormann Ulrich; Henss Anja; Rohnke Marcus; Bauer Natali; Mueller Robert; Deutsch Andreas; Ignatius Anita; Duerselen Lutz; Langheinrich Alexander; Lips Katrin S; Schnettler Reinhard; Heiss Christian^*

来源：Histochemistry and Cell Biology, 2015, 144(5): 491-507.

DOI：10.1007/s00418-015-1356-9

• Osteoporosis
• Rat model
• Malnutrition
• Extracellular matrix
• ToF-SIMS
• Modeling
• Osteocytes

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.

• 出版日期2015-11