Effect of human adipose-derived mesenchymal stem cells preconditioned with cobalt chloride for hypoxia induction on ovariectomy-induced osteoporosis

authors:

avatar Mahmoud Gorji-Valokola , avatar Hamideh Babaloo , avatar Hamed Kheradmand , avatar SOMAYE fallahnezhad , *


how to cite: Gorji-Valokola M, Babaloo H, Kheradmand H, fallahnezhad S. Effect of human adipose-derived mesenchymal stem cells preconditioned with cobalt chloride for hypoxia induction on ovariectomy-induced osteoporosis. koomesh. 2023;25(6):e152867. 

Abstract

Introduction: Osteoporosis (OP) is a chronic metabolic disease. Cobalt (II) chloride (CoCl2) induces favorable effects on hAD-MSCs (human Adipose-Derived Mesenchymal Stem Cells) function. This study aimed to assess the effects of CoCl2-preconditioned hAD-MSCs injection for hypoxia induction in female rats with ovariectomy-induced OP. Materials and Methods: 24 adult female rats were subjected to bilateral ovariectomy. After 3.5 months, the OP progression was evaluated using CT scanning procedures with densitometric evaluation. Then, the animals were divided into 3 groups: sham (control), normoxia, and hypoxia groups receiving PBS (Phosphate Buffered Saline), hAD-MSCs, and 100 µM CoCl2-exposed hAD-MSCs for 48 h, respectively, via the tail vein. After 2 months, to investigate the hypoxia-inducing factor-1α (HIF-1α) by western blot analysis and to assess growth factors Insulin-like Growth Factor (IGF1) and Transforming Growth Factor Beta (TGFβ) and pro-inflammatory cytokines Tumor Necrosis Factor Alpha (TNFα) and Interleukin-1beta (IL-1β) using the ELISA (Enzyme-Linked Immunosorbent Assay) method, sampling of right and left tibia bone tissue markers was respectively done. Results: In the group receiving 100 µM CoCl2-pretreated hAD-MSCs for 48 h, compared to the groups receiving normoxia cells and PBS, an increase in the expression of HIF-1α (P> 0.01 and P> 0.001), IGF-I (P> 0.01 and P>0.001), and TGF-β (P> 0.05 and P> 0.01), and a decrease in the expression of TNF-α and IL-1β (P> 0.001 and P>0.01) were significantly observed in right and left tibia bone, respectively. Conclusion: CoCl2 led to increased efficiency and effectiveness of CoCl2-pretreated hAD-MSCs in reducing the expression of pro-inflammatory cytokines and increasing growth factors through increasing the expression of HIF-1α.

References

  • 1.

    Loi F, Crdova LA, Pajarinen J, Lin TH, Yao Z, Goodman SB. Inflammation, fracture and bone repair. Bone 2016; 86: 119-130.

  • 2.

    Faienza MF, Ventura A, Marzano F, Cavallo L. Postmenopausal osteoporosis: the role of immune system cells. Clin Dev Immunol 2013; 2013: 575936.

  • 3.

    Manolagas SC, O'Brien CA, Almeida M. The role of estrogen and androgen receptors in bone health and disease. Nat Rev Endocrinol 2013; 9: 699-712.

  • 4.

    Bonjour JP, Chevalley T. Pubertal timing, bone acquisition, and risk of fracture throughout life. Endocr Rev 2014; 35: 820-847.

  • 5.

    Zallone A. Direct and indirect estrogen actions on osteoblasts and osteoclasts. Ann N Y Acad Sci 2006; 1068: 173-179.

  • 6.

    Callewaert F, Boonen S, Vanderschueren D. Sex steroids and the male skeleton: a tale of two hormones. Trends Endocrinol Metab 2010; 21: 89-95.

  • 7.

    Rodrguez-Fuentes DE, Fernndez-Garza LE, Samia-Meza JA, Barrera-Barrera SA, Caplan AI, Barrera-Saldaa HA. Mesenchymal stem cells current clinical applications: a systematic review. Arch Med Res 2021; 52: 93-101.

  • 8.

    Jiang Y, Zhang P, Zhang X, Lv L, Zhou Y. Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis. Cell Prolif 2021; 54: e12956.

  • 9.

    Barry FP, Murphy JM. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 2004; 36: 568-584.

  • 10.

    Jahangir AA. Washington health policy fellows. Bonegraft substitutes in orthopaedic surgery. AAOS Now 2008; 2: 1.

  • 11.

    Hu C, Li L. Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. J Cell Mol Med 2018; 22: 1428-1442.

  • 12.

    Di Mattia M, Mauro A, Citeroni MR, Dufrusine B, Peserico A, Russo V, et al. Insight into Hypoxia Stemness Control. Cells 2021; 10.

  • 13.

    Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell 2012; 148: 399-408.

  • 14.

    Nowak-Stpniowska A, Osuchowska PN, Fiedorowicz H, Trafny EA. Insight in hypoxia-mimetic agents as potential tools for mesenchymal stem cell priming in regenerative medicine. Stem Cells Int 2022; 2022: 8775591.

  • 15.

    Zhang J, Feng Z, Wei J, Yu Y, Luo J, Zhou J, et al. Repair of critical-sized mandible defects in aged rat using hypoxia preconditioned BMSCs with Up-regulation of Hif-1. Int J Biol Sci 2018; 14: 449-460.

  • 16.

    Vafaei A, Khorasani F, Seraj Z, Miladi-Gorji H, Rashidy-Pour A. Effects of forced exercise on object location memory and anxiety behaviour in morphine dependent ovariectomized rats. Koomesh 2020; 22. (Persian)##https://doi.org/10.29252/koomesh.22.4.704.

  • 17.

    Fallahnezhad S, Amini A, Hajihossainlou B, Chien S, Dadras S, Rezaei F, et al. Combined effects of photobiomodulation and alendronate on viability of osteoporotic bone marrow-derived mesenchymal stem cells. J Photochem Photobiol B 2018; 182: 77-84.

  • 18.

    Khatami SS, Tavakoli F, Bagheri H, Salarinia R, Hesari A, GHasemi F. Effects of fibromodulin protein expression on NFkB and TGF signaling pathways in liver cancer cells. 2020. (Persian)##https://doi.org/10.29252/koomesh.22.3.529.

  • 19.

    Chen Y, Zhao Q, Yang X, Yu X, Yu D, Zhao W. Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth. Cell Stress Chaperones 2019; 24: 527-538.

  • 20.

    Fallahnezhad S, Ghorbani-Taherdehi F, Sahebkar A, Nadim A, Kafashzadeh M, Kafashzadeh M, et al. Potential neuroprotective effect of nanomicellar curcumin on learning and memory functions following subacute exposure to bisphenol A in adult male rats. Metab Brain Dis 2023.

  • 21.

    Valokola MG, Karimi G, Razavi BM, Kianfar M, Jafarian AH, Jaafari MR, et al. The protective activity of nanomicelle curcumin in bisphenol A-induced cardiotoxicity following subacute exposure in rats. Environ Toxicol 2019; 34: 319-329.

  • 22.

    Fallahnezhad S, Piryaei A, Darbandi H, Amini A, Ghoreishi SK, Jalalifirouzkouhi R, et al. Effect of low-level laser therapy and oxytocin on osteoporotic bone marrow-derived mesenchymal stem cells. J Cell Biochem 2018; 119: 983-997.

  • 23.

    Antebi B, Pelled G, Gazit D. Stem cell therapy for osteoporosis. Curr Osteoporos Rep 2014; 12: 41-47.

  • 24.

    Berebichez-Fridman R, Montero-Olvera PR. Sources and clinical applications of mesenchymal stem cells: State-of-the-art review. Sultan Qaboos Univ Med J 2018; 18: e264-e277.

  • 25.

    Kolios G, Moodley Y. Introduction to stem cells and regenerative medicine. Respiration 2013; 85: 3-10.

  • 26.

    Cui L, Liu B, Liu G, Zhang W, Cen L, Sun J, et al. Repair of cranial bone defects with adipose derived stem cells and coral scaffold in a canine model. Biomaterials 2007; 28: 5477-5486.

  • 27.

    Vajgel A, Mardas N, Farias BC, Petrie A, Cimes R, Donos N. A systematic review on the critical size defect model. Clin Oral Implants Res 2014; 25: 879-893.

  • 28.

    Noordin S, Allana S, Umer M, Jamil M, Hilal K, Uddin N. Unicameral bone cysts: Current concepts. Ann Med Surg (Lond) 2018; 34: 43-49.

  • 29.

    Asnaashari M, Safavi N. Application of Low level Lasers in Dentistry (Endodontic). J Lasers Med Sci 2013; 4: 57-66.

  • 30.

    Valchinov ES, Pallikarakis NE. Design and testing of low intensity laser biostimulator. Biomed Eng Online 2005; 4: 5.

  • 31.

    Yuan LL, Guan YJ, Ma DD, Du HM. Optimal concentration and time window for proliferation and differentiation of neural stem cells from embryonic cerebral cortex: 5% oxygen preconditioning for 72 hours. Neural Regen Res 2015; 10: 1516-1522.

  • 32.

    Ye X, Zhang P, Xue S, Xu Y, Tan J, Liu G. Adipose-derived stem cells alleviate osteoporosis by enhancing osteogenesis and inhibiting adipogenesis in a rabbit model. Cytotherapy 2014; 16: 1643-1655.

  • 33.

    Da Silva D, Crous A, Abrahamse H. Photobiomodulation: an effective approach to enhance proliferation and differentiation of adipose-derived stem cells into osteoblasts. Stem Cells Int 2021; 2021: 8843179.

  • 34.

    Mo Q, Zhang W, Zhu A, Backman LJ, Chen J. Regulation of osteogenic differentiation by the pro-inflammatory cytokines IL-1 and TNF-: current conclusions and controversies. Hum Cell 2022; 35: 957-971.

  • 35.

    Kitaura H, Kimura K, Ishida M, Kohara H, Yoshimatsu M, Takano-Yamamoto T. Immunological reaction in TNF--mediated osteoclast formation and bone resorption in vitro and in vivo. Clin Dev Immunol 2013; 2013: 181849.

  • 36.

    Dalle Carbonare L, Innamorati G, Valenti MT. Transcription factor Runx2 and its application to bone tissue engineering. Stem Cell Rev Rep 2012; 8: 891-897.

  • 37.

    Garg P, Mazur MM, Buck AC, Wandtke ME, Liu J, Ebraheim NA. Prospective review of mesenchymal stem cells differentiation into osteoblasts. Orthop Surg 2017; 9: 13-19.

  • 38.

    Mohyeldin A, Garzn-Muvdi T, Quiones-Hinojosa A. Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell 2010; 7: 150-161.

  • 39.

    Berniakovich I, Giorgio M. Low oxygen tension maintains multipotency, whereas normoxia increases differentiation of mouse bone marrow stromal cells. Int J Mol Sci 2013; 14: 2119-2134.

  • 40.

    Kim DS, Ko YJ, Lee MW, Park HJ, Park YJ, Kim DI, et al. Effect of low oxygen tension on the biological characteristics of human bone marrow mesenchymal stem cells. Cell Stress Chaperones 2016; 21: 1089-1099.

  • 41.

    Osathanon T, Vivatbutsiri P, Sukarawan W, Sriarj W, Pavasant P, Sooampon S. Cobalt chloride supplementation induces stem-cell marker expression and inhibits osteoblastic differentiation in human periodontal ligament cells. Arch Oral Biol 2015; 60: 29-36.

  • 42.

    Di Mattia M, Mauro A, Delle Monache S, Pulcini F, Russo V, Berardinelli P, et al. Hypoxia-mimetic CoCl(2) agent enhances pro-angiogenic activities in ovine amniotic epithelial cells-derived conditioned medium. Cells 2022; 11.

  • 43.

    Wagegg M, Gaber T, Lohanatha FL, Hahne M, Strehl C, Fangradt M, et al. Hypoxia promotes osteogenesis but suppresses adipogenesis of human mesenchymal stromal cells in a hypoxia-inducible factor-1 dependent manner. PLoS One 2012; 7: e46483.

  • 44.

    Oladipupo S, Hu S, Kovalski J, Yao J, Santeford A, Sohn RE, et al. VEGF is essential for hypoxia-inducible factor-mediated neovascularization but dispensable for endothelial sprouting. Proc Natl Acad Sci USA 2011; 108: 13264-13249.

  • 45.

    Stegen S, van Gastel N, Eelen G, Ghesquire B, D'Anna F, Thienpont B, et al. HIF-1 promotes glutamine-mediated redox homeostasis and glycogen-dependent bioenergetics to support postimplantation bone cell survival. Cell Metab 2016; 23: 265-279.

  • 46.

    Komori T. Regulation of bone development and extracellular matrix protein genes by RUNX2. Cell Tissue Res 2010; 339: 189-195.

  • 47.

    Zou ML, Chen ZH, Teng YY, Liu SY, Jia Y, Zhang KW, et al. The smad dependent TGF- and BMP signaling pathway in bone remodeling and therapies. Front Mol Biosci 2021; 8: 593310.

  • 48.

    Liao LN, Li CI, Wu FY, Yang CW, Lin CH, Liu CS, et al. Important gene-gene interaction of TNF- and VDR on osteoporosis in community-dwelling elders. PLoS One 2019; 14: e0226973.