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Osteoblast-Based Therapy—A New Approach for Bone Repair in Osteoporosis: Pre-Clinical Setting

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Osteoporosis is a metabolic bone disease characterized by low bone density resulting in increased fracture susceptibility. This research was constructed to uncover the potential therapeutic application of osteoblasts transplantation, generated upon culturing male rat bone marrow-derived mesenchymal stem cells (BM-MSCs) in osteogenic medium (OM), OM containing gold (Au-NPs) or gold/hydroxyapatite (Au/HA-NPs) nanoparticles, in ovariectomized rats to counteract osteoporosis.

Methods:

Forty rats were randomized into: (1) negative control, (2) osteoporotic rats, whereas groups (3), (4) and (5) constituted osteoporotic rats treated with osteoblasts yielded from culturing BM-MSCs in OM, OM plus Au-NPs or Au/HA-NPs, respectively. After 3 months, osterix (OSX), bone alkaline phosphatase (BALP), sclerostin (SOST) and bone sialoprotein (BSP) serum levels were assessed. In addition, gene expression levels of cathepsin K, receptor activator of nuclear factor-κb ligand (RANKL), osteoprotegerin (OPG) and RANKL/OPG ratio were evaluated using real-time PCR. Moreover, histological investigation of femur bone tissues in different groups was performed. The homing of implanted osteoblasts to the osteoporotic femur bone of rats was documented by Sex determining region Y gene detection in bone tissue.

Results:

Our results indicated that osteoblasts infusion significantly blunted serum BALP, BSP and SOST levels, while significantly elevated OSX level. Also, they brought about significant down-regulation in gene expression levels of cathepsin K, RANKL and RANKL/OPG ratio versus untreated osteoporotic rats. Additionally, osteoblasts nidation could restore bone histoarchitecture.

Conclusion:

These findings offer scientific evidence that transplanting osteoblasts in osteoporotic rats regains the homeostasis of the bone remodeling cycle, thus providing a promising treatment strategy for primary osteoporosis.

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Acknowledgements

The authors gratefully appreciate the financial support of the National Research Centre, Egypt (Thesis fund no. 71511). Also, the authors express sincere appreciation to Prof. Adel Bakeer Kholousy, Professor of Pathology, Faculty of Veterinary Medicine, Cairo University for his kind participation in histological examination of this study.

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Authors and Affiliations

  1. Hormones Department, Medical Research Division, National Research Centre, 33 EL Bohouth St. (former EL –Tahrir st.)-Dokki, Giza, 12622, Egypt

    Nadia Samy Mahmoud, Hadeer Ahmed Aglan & Hanaa Hamdy Ahmed

  2. Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, 33 EL Bohouth St. (former EL –Tahrir st.)-Dokki, Giza, 12622, Egypt

    Nadia Samy Mahmoud, Hadeer Ahmed Aglan & Hanaa Hamdy Ahmed

  3. Biochemistry Department, Faculty of Science, Ain Shams University, El-Khalyfa El-Ma’moun St., Abbasya, Cairo, 11566, Egypt

    Mohamed Ragaa Mohamed & Mohamed Ahmed Mohamed Ali

  4. Medical Molecular Genetics Department, Human Genetics and Genome Researches Division, National Research Centre, 33 EL Bohouth St. (former EL –Tahrir St.)-Dokki, Giza, 12622, Egypt

    Khalda Sayed Amr

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  1. Nadia Samy Mahmoud
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  2. Mohamed Ragaa Mohamed
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Correspondence to Nadia Samy Mahmoud.

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Ethical statement

This study was conducted according to the ethical considerations for the experimental animals and approved by the Ethical Committee for Medical Research of the National Research Centre, Giza, Egypt, which follows the recommendations of the National Institutes of Health Guide for Care and Use of Laboratory Animals (Approval No.15106).

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Mahmoud, N.S., Mohamed, M.R., Ali, M.A.M. et al. Osteoblast-Based Therapy—A New Approach for Bone Repair in Osteoporosis: Pre-Clinical Setting. Tissue Eng Regen Med 17, 363–373 (2020). https://doi.org/10.1007/s13770-020-00249-5

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  • DOI: https://doi.org/10.1007/s13770-020-00249-5

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