The Implication of Altered DKK1/LRP/β-catenin Signaling in Dexamethasone Induced Bone Remodeling Disruption: In Silico and In Vivo Studies in Male Rats
Maher, A., Saleh, S., Ghareeb, D., Sheta, E., Nabil, M., Younis, F., Masoud, A. (2024). The Implication of Altered DKK1/LRP/β-catenin Signaling in Dexamethasone Induced Bone Remodeling Disruption: In Silico and In Vivo Studies in Male Rats. EKB Journal Management System, 16(1), 23-46. doi: 10.21608/eajbsc.2024.335612
Adham M. Maher; Samar R. Saleh; Doaa A. Ghareeb; Eman Sheta; Mohamed Nabil; Fatema A. Younis; Aliaa A. Masoud. "The Implication of Altered DKK1/LRP/β-catenin Signaling in Dexamethasone Induced Bone Remodeling Disruption: In Silico and In Vivo Studies in Male Rats". EKB Journal Management System, 16, 1, 2024, 23-46. doi: 10.21608/eajbsc.2024.335612
Maher, A., Saleh, S., Ghareeb, D., Sheta, E., Nabil, M., Younis, F., Masoud, A. (2024). 'The Implication of Altered DKK1/LRP/β-catenin Signaling in Dexamethasone Induced Bone Remodeling Disruption: In Silico and In Vivo Studies in Male Rats', EKB Journal Management System, 16(1), pp. 23-46. doi: 10.21608/eajbsc.2024.335612
Maher, A., Saleh, S., Ghareeb, D., Sheta, E., Nabil, M., Younis, F., Masoud, A. The Implication of Altered DKK1/LRP/β-catenin Signaling in Dexamethasone Induced Bone Remodeling Disruption: In Silico and In Vivo Studies in Male Rats. EKB Journal Management System, 2024; 16(1): 23-46. doi: 10.21608/eajbsc.2024.335612

The Implication of Altered DKK1/LRP/β-catenin Signaling in Dexamethasone Induced Bone Remodeling Disruption: In Silico and In Vivo Studies in Male Rats

Egyptian Academic Journal of Biological Sciences. C, Physiology and Molecular Biology
Volume 16, Issue 1, June 2024, Page 23-46  XML PDF (1.41 MB)
Document Type: Original Article
DOI: 10.21608/eajbsc.2024.335612
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Authors
Adham M. Maherorcid 1; Samar R. Saleh1; Doaa A. Ghareeb1; Eman Sheta2; Mohamed Nabil3; Fatema A. Younis1; Aliaa A. Masoud1
1Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt.
2Department of Pathology, Faculty of Medicine, Alexandria University.
3Pharmacology Department, Faculty of Pharmacy, New Valley University, Kharga 72511, Egypt.
Abstract
Background: Long-term glucocorticoid administration represents the main source of 2ry osteoporosis, jeopardizing bone to fracture and loss. This study presents an innovation regarding the alterations in the osteoporotic Wnt/β-catenin signal encouraged by dexamethasone through studying some markers implicated in the proliferation and differentiation of the major bone remodeling cells using in silico and in vivo studies. Methods and Results: Docked models were used to visualize and evaluate the binding of dexamethasone (DEXA) towards main bone remodeling modulators. Regarding the in vivo study, sixteen Sprague-Dawley adult males were designated into a control group administered saline, and an osteoporosis-induced group was administered 1 mg/kg DEXA intraperitoneally daily for 6 weeks. The molecular docking demonstrated binding and interactions between DEXA and main bone remodeling targets. DEXA treatment caused osteoporotic changes in femoral microscopy, increased femoral oxidative stress, elevated proliferation markers, raised osteoblast differentiation inhibitor, diminished markers for osteoblasts differentiation, and increased markers for differentiation of osteoclasts and adipocytes. Conclusions: Glucocorticoid-induced osteoporosis is manifested through an intensified proliferation of HSCs and MSCs via escalating and changing the Wnt signaling, which acts as a communicator between both cell populations. These alterations brought about the track-change of MSCs differentiation from the osteoblastic to the adipocytic track and accelerated osteoclastic differentiation.
Keywords
Glucocorticoids; HSCs; MSCs; Oxidative stress; Osteoporosis; Wnt signaling
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