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CC BY 4.0 · Eur J Dent 2023; 17(02): 319-329
DOI: 10.1055/s-0042-1745768
Original Article

Bone Remodeling in Mandible of Wistar Rats with Diabetes Mellitus and Osteoporosis

Nike Hendrijantini
1   Department of Prosthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
Yonatan Christian Suisan
2   Resident of Prosthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
Rizko Wira Artha Megantara
2   Resident of Prosthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
Bambang Agustono Satmoko Tumali
1   Department of Prosthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
Mefina Kuntjoro
1   Department of Prosthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
Muhammad Dimas Aditya Ari
1   Department of Prosthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
Ratri Maya Sitalaksmi
1   Department of Prosthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
Guang Hong 
3   Division for Globalization Initiative, Graduate School of Dentistry, Tohoku University, Sendai, Japan
› Author Affiliations Funding This research was supported by Universitas Airlangga International Collaboration Research Grant with number 212/UN3/2021.
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Abstract

Objectives This study aimed to determine some of bone molecular expressions and its possible bone remodeling pathway between diabetes mellitus (DM) and osteoporosis model in the mandibular bone of Wistar rats.

Materials and Methods Twenty-seven female Wistar rats were divided randomly into control and treatment groups. Treatment groups were injected with streptozotocin intraperitoneally to induce DM (P1) and underwent bilateral ovariectomy to generate osteoporosis (P2). All groups were terminated after 12 weeks. Immunohistochemical and hematoxylin–eosin staining were performed to determine the expression of Runt-related transcription factor 2 (RUNX2), Osterix, vascular endothelial growth factor (VEGF), receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and observed the osteoblast and osteoclast. Statistical analysis was performed using one-way analysis of variance.

Results The lowest mean of RUNX2 and VEGF expression was found in the P2 group. The lowest mean of Osterix expression was found in the P1 group. Both P1 and P2 groups of osteoblast/osteoclast ratio were decreased. There were no significant differences in the expression of TRAP between all groups; however, increased expression of RANKL/OPG ratio was only found in the P2 group.

Conclusion DM and osteoporosis induce changes in the bone remodeling pathway which are represented by a decrease in osteoblast biomarkers and an increase in osteoclast biomarkers.

Keywords

diabetes mellitus - osteoporosis - bone remodeling - medicine


Publication History

Article published online:
04 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Giro G, Chambrone L, Goldstein A. et al. Impact of osteoporosis in dental implants: a systematic review. World J Orthop 2015; 6 (02) 311-315
    CrossrefPubMedGoogle Scholar
  • 2 Hendrijanti N, Rostiny R, Kuntjoro M. et al. The effect of low-level estrogen in mandibular bone: an in vivo study. Dent Res J (Isfahan) 2019; 16 (02) 65-70
    CrossrefPubMedGoogle Scholar
  • 3 Meza Maurício J, Miranda TS, Almeida ML, Silva HD, Figueiredo LC, Duarte PM. An umbrella review on the effects of diabetes on implant failure and peri-implant diseases. Braz Oral Res 2019; 33 (suppl 1): e070
    CrossrefPubMedGoogle Scholar
  • 4 International Diabetes Federation. IDF Diabetes Atlas. 6th ed.. Belgium: International Diabetes Federation; 2013
    Google Scholar
  • 5 Wongdee K, Charoenphandhu N. Osteoporosis in diabetes mellitus: possible cellular and molecular mechanisms. World J Diabetes 2011; 2 (03) 41-48
    CrossrefPubMedGoogle Scholar
  • 6 Chrcanovic BR, Albrektsson T, Wennerberg A. Diabetes and oral implant failure: a systematic review. J Dent Res 2014; 93 (09) 859-867
    CrossrefPubMedGoogle Scholar
  • 7 Kementerian Kesehatan RI. Waspada Diabetes Eat Well Live Well. Infodatin Pus. Data dan Inf. Kementerian Kesehatan RI. 2015
    PubMedGoogle Scholar
  • 8 World Health Organization. Global report on diabetes. 2014; 58: 1-88
    PubMedGoogle Scholar
  • 9 Dubey RK, Gupta DK, Singh AK. Dental implant survival in diabetic patients; review and recommendations. Natl J Maxillofac Surg 2013; 4 (02) 142-150
    CrossrefPubMedGoogle Scholar
  • 10 Dumitru N, Carsote M, Cocolos A. et al. Metabolic and bone profile in postmenopausal women with and without type 2 diabetes: a cross-sectional study. Rom J Intern Med 2019; 57 (01) 61-67
    PubMedGoogle Scholar
  • 11 Al-Maweri SAA, Ismail NM, Ismail AR, Al-Ghashm A. Prevalence of oral mucosal lesions in patients with type 2 diabetes attending Hospital Universiti Sains Malaysia. Malays J Med Sci 2013; 20 (04) 39-46
    PubMedGoogle Scholar
  • 12 Javed F, Romanos GE. Impact of diabetes mellitus and glycemic control on the osseointegration of dental implants: a systematic literature review. J Periodontol 2009; 80 (11) 1719-1730
    CrossrefPubMedGoogle Scholar
  • 13 Oates TW, Huynh-Ba G, Vargas A, Alexander P, Feine J. A critical review of diabetes, glycemic control, and dental implant therapy. Clin Oral Implants Res 2013; 24 (02) 117-127
    CrossrefPubMedGoogle Scholar
  • 14 Piccinin MA, Khan ZA. Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications. Adipocyte 2014; 3 (04) 263-272
    CrossrefPubMedGoogle Scholar
  • 15 Ferdous HS, Afsana F, Qureshi NK, Rouf RSB. Osteoporosis: a review. BIRDEM Med J 2016; 5 (01) 30-36
    CrossrefGoogle Scholar
  • 16 Kohli SS, Kohli VS. Role of RANKL-RANK/osteoprotegerin molecular complex in bone remodeling and its immunopathologic implications. Indian J Endocrinol Metab 2011; 15 (03) 175-181
    CrossrefPubMedGoogle Scholar
  • 17 Kementerian Kesehatan RI. Data & Kondisi Penyakit Osteoporosis di Indonesia. Infodatin Pus. Data dan Inf. Kementerian Kesehatan RI. 2015
    PubMedGoogle Scholar
  • 18 Cochran DL. Inflammation and bone loss in periodontal disease. J Periodontol 2008; 79 (8, Suppl): 1569-1576
    CrossrefPubMedGoogle Scholar
  • 19 Li Z, Li C, Zhou Y. et al. Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells. Am J Physiol Endocrinol Metab 2016; 310 (05) E355-E366
    CrossrefPubMedGoogle Scholar
  • 20 Fowlkes JL, Bunn RC, Liu L. et al. Runt-related transcription factor 2 (RUNX2) and RUNX2-related osteogenic genes are down-regulated throughout osteogenesis in type 1 diabetes mellitus. Endocrinology 2008; 149 (04) 1697-1704
    CrossrefPubMedGoogle Scholar
  • 21 Miranda C, Giner M, Montoya MJ, Vázquez MA, Miranda MJ, Pérez-Cano R. Influence of high glucose and advanced glycation end-products (AGES) levels in human osteoblast-like cells gene expression. BMC Musculoskelet Disord 2016; 17: 377
    CrossrefPubMedGoogle Scholar
  • 22 Wallner C, Schira J, Wagner JM. et al. Application of VEGFA and FGF-9 enhances angiogenesis, osteogenesis and bone remodeling in type 2 diabetic long bone regeneration. PLoS One 2015; 10 (03) e0118823
    CrossrefPubMedGoogle Scholar
  • 23 Wu YY, Xiao E, Graves DT. Diabetes mellitus related bone metabolism and periodontal disease. Int J Oral Sci 2015; 7 (02) 63-72
    CrossrefPubMedGoogle Scholar
  • 24 Chen Y, Hu Y, Yang L. et al. Runx2 alleviates high glucose-suppressed osteogenic differentiation via PI3K/AKT/GSK3β/β-catenin pathway. Cell Biol Int 2017; 41 (08) 822-832
    CrossrefPubMedGoogle Scholar
  • 25 Rios-Arce ND, Dagenais A, Feenstra D. et al. Loss of interleukin-10 exacerbates early Type-1 diabetes-induced bone loss. J Cell Physiol 2020; 235 (03) 2350-2365
    CrossrefPubMedGoogle Scholar
  • 26 Fan J-Z, Yang L, Meng GL. et al. Estrogen improves the proliferation and differentiation of hBMSCs derived from postmenopausal osteoporosis through notch signaling pathway. Mol Cell Biochem 2014; 392 (1-2): 85-93
    CrossrefPubMedGoogle Scholar
  • 27 Raehtz S, Bierhalter H, Schoenherr D, Parameswaran N, McCabe LR. Estrogen deficiency exacerbates type 1 diabetes-induced bone TNF-α expression and osteoporosis in female mice. Endocrinology 2017; 158 (07) 2086-2101
    CrossrefPubMedGoogle Scholar
  • 28 Catalfamo DL, Britten TM, Storch DL, Calderon NL, Sorenson HL, Wallet SM. Hyperglycemia induced and intrinsic alterations in type 2 diabetes-derived osteoclast function. Oral Dis 2013; 19 (03) 303-312
    CrossrefPubMedGoogle Scholar
  • 29 Khosla S, Oursler MJ, Monroe DG. Estrogen and the skeleton. Trends Endocrinol Metab 2012; 23 (11) 576-581
    CrossrefPubMedGoogle Scholar
  • 30 Senel K, Baykal T, Seferoglu B. et al. Circulating vascular endothelial growth factor concentrations in patients with postmenopausal osteoporosis. Arch Med Sci 2013; 9 (04) 709-712
    CrossrefPubMedGoogle Scholar
  • 31 Zhang Q, Fang W, Ma L, Wang ZD, Yang YM, Lu YQ. VEGF levels in plasma in relation to metabolic control, inflammation, and microvascular complications in type-2 diabetes: a cohort study. Medicine (Baltimore) 2018; 97 (15) e0415
    CrossrefPubMedGoogle Scholar
  • 32 Hendrijantini N, Rostiny R, Kurdi A. et al. Molecular triad RANK/RANKL/OPG in mandible and femur of wistar rats (Rattus norvegicus) with type 2 diabetes mellitus. Recent Adv Biol Med. 2019; 25 (05) 11090
    Google Scholar
  • 33 Hu Z, Ma C, Liang Y, Zou S, Liu X. Osteoclasts in bone regeneration under type 2 diabetes mellitus. Acta Biomater 2019; 84: 402-413
    CrossrefPubMedGoogle Scholar
  • 34 Sassi F, Buondonno I, Luppi C. et al. Type 2 diabetes affects bone cells precursors and bone turnover. BMC Endocr Disord 2018; 18 (01) 55
    CrossrefPubMedGoogle Scholar
  • 35 Li Y, Shrestha A, Zhang H. et al. Impact of diabetes mellitus simulations on bone cell behavior through in vitro models. J Bone Miner Metab 2020; 38 (05) 607-619
    CrossrefPubMedGoogle Scholar
  • 36 Xu F, Dong Y, Huang X. et al. Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes. Mol Med Rep 2014; 10 (04) 1935-1941
    CrossrefPubMedGoogle Scholar
  • 37 Azizieh FY, Shehab D, Jarallah KA, Gupta R, Raghupathy R. Circulatory levels of RANKL, OPG, and oxidative stress markers in postmenopausal women with normal or low bone mineral density. Biomark Insights 2019; 14: 1177271919843825
    CrossrefPubMedGoogle Scholar
  • 38 Lu R, Zheng Z, Yin Y, Jiang Z. Genistein prevents bone loss in type 2 diabetic rats induced by streptozotocin. Food Nutr Res 2020; 64: 1-12
    Google Scholar
  • 39 Halleen JM, Alatalo SL, Suominen H, Cheng S, Janckila AJ, Väänänen HK. Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res 2000; 15 (07) 1337-1345
    CrossrefPubMedGoogle Scholar
  • 40 Miyazaki T, Matsunaga T, Miyazaki S, Hokari S, Komoda T. Changes in receptor activator of nuclear factor-kappaB, and its ligand, osteoprotegerin, bone-type alkaline phosphatase, and tartrate-resistant acid phosphatase in ovariectomized rats. J Cell Biochem 2004; 93 (03) 503-512
    CrossrefPubMedGoogle Scholar
  • 41 Verit FF, Yazgan P, Geyikli I, Zer Y, Çelik A. Diagnostic value of TRAP 5b activity in postmenopausal osteoporosis. J Turk Ger Gynecol Assoc 2006; 7: 120-124
    Google Scholar
  • 42 Kim M, Kim HS, Kim JH. et al. Chaenomelis fructus inhibits osteoclast differentiation by suppressing NFATc1 expression and prevents ovariectomy-induced osteoporosis. BMC Complement Med Ther 2020; 20 (01) 35
    CrossrefPubMedGoogle Scholar