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01-06-2023 | Tooth Extraction | Research

Influence of age and gender on alveolar bone healing post tooth extraction in 129 Sv mice: a microtomographic, histological, and biochemical characterization

Authors: Claudia Cristina Biguetti, Bhuvana Lakkasetter Chandrashekar, Gustavo Baroni Simionato, Nataira Regina Momesso, Marco Antonio Hungaro Duarte, Danieli C. Rodrigues, Mariza Akemi Matsumoto

Published in: Clinical Oral Investigations | Issue 8/2023

Abstract

Objectives

To analyze the effect of biological sex and aging on craniofacial bone features in 129 Sv mice and their influence on dental socket healing post tooth extraction.

Materials and methods

A total of 52 129 Sv mice were used, of which 28 were young (3–4 months) and 24 were aged (17–18 months), equally distributed according to biological sex. After an upper right incisor extraction, mice specimens were collected at 7, 14, and 21-days post-surgery for microtomographic (microCT) and comprehensive histological analysis. Mandible, skull bones, and maxillae at 21 days were analyzed by microCT, while blood plasma samples were collected for the detection of key bone turnover markers (P1NP and CTX-1) by enzyme-linked immunosorbent (ELISA) assay.

Results

Aged females depicted significantly decreased mineralized bone content in alveolar sockets in comparison to young females and aged males at day 7, and aged males at day 14. Mandible RCA and Ma.AR of aged females were also significantly decreased in comparison with young females. Histological evaluation revealed that all alveolar sockets healed at 21 days with inflammation resolution and deposition of new bone. Immunohistochemistry for TRAP revealed increased area density for osteoclasts in alveolar sockets of aged females when compared to young females at 21 days. While a significant increase in CTX-1 levels was detected in blood plasma of aged females when compared to young females, P1NP levels did not significantly change between young and older females. No significant changes were observed for males.

Conclusions

Age and gender can significantly affect craniofacial bones of 129 Sv mice, especially maxilla and mandible in females. Considering the altered bone resorption parameters and delayed alveolar bone healing in older females, careful deliberation is necessary during development of pre-clinical models for craniofacial research.

Clinical relevance

Aging can be a contributing factor to slower bone healing in craniofacial bones. However, there are no sufficient experimental studies that have addressed this phenomenon along with biological sex taken into consideration.

Martin DE, Torrance BL, Haynes L, Bartley JM (2021) Targeting aging: lessons learned from immunometabolism and cellular senescence. Front Immunol 12:1–7. https://doi.org/10.3389/fimmu.2021.714742CrossRef

Adams DJ, Rowe DW, Ackert-Bicknell CL (2016) Genetics of aging bone. Mamm Genome 27:367–380. https://doi.org/10.1007/s00335-016-9650-yCrossRefPubMedPubMedCentral

Gibon E, Lu L, Goodman SB (2016) Aging, inflammation, stem cells, and bone healing. Stem Cell Res Ther 7:1–7. https://doi.org/10.1186/s13287-016-0300-9CrossRef

Currey JD, Brear K, Zioupos P (1996) The effects of ageing and changes in mineral content in degrading the toughness of human femora. J Biomech 29:257–260. https://doi.org/10.1016/0021-9290(95)00048-8CrossRefPubMed

Milovanovic P, Zimmermann EA, Riedel C et al (2015) Multi-level characterization of human femoral cortices and their underlying osteocyte network reveal trends in quality of young, aged, osteoporotic and antiresorptive-treated bone. Biomaterials 45:46–55. https://doi.org/10.1016/j.biomaterials.2014.12.024CrossRefPubMed

Biguetti CC, Couto MCR, Silva ACR et al (2020) New surgical model for bone–muscle injury reveals age and gender-related healing patterns in the 5 lipoxygenase (5LO) knockout mouse. Front Endocrinol (Lausanne) 11:1–20. https://doi.org/10.3389/fendo.2020.00484CrossRef

Elani HW, Starr JR, Da Silva JD, Gallucci GO (2018) Trends in dental implant use in the U.S., 1999–2016, and Projections to 2026. J Dent Res 97:1424–1430. https://doi.org/10.1177/0022034518792567CrossRefPubMedPubMedCentral

Strube P, Sentuerk U, Riha T et al (2008) Influence of age and mechanical stability on bone defect healing: age reverses mechanical effects. Bone 42:758–764. https://doi.org/10.1016/j.bone.2007.12.223CrossRefPubMed

Lang TF (2011) The bone-muscle relationship in men and women. J Osteoporos 2011:1–4. https://doi.org/10.4061/2011/702735CrossRef

10.

Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16:626–638. https://doi.org/10.1038/nri.2016.90CrossRefPubMed

11.

Khosla S, Monroe DG (2018) Regulation of bone metabolism by sex steroids. Cold Spring Harb Perspect Med 8:a031211. https://doi.org/10.1101/cshperspect.a031211CrossRefPubMedPubMedCentral

12.

Akabane C, Pabisch S, Wagermaier W et al (2021) The effect of aging on the nanostructure of murine alveolar bone and dentin. J Bone Miner Metab 39:757–768. https://doi.org/10.1007/s00774-021-01227-0CrossRefPubMed

13.

Ono R, Abe M, Koike N et al (2021) Quantitative morphometric analysis of molar teeth and alveolar bone using micro-computed tomography in aged mice. J Oral Biosci 63:265–270. https://doi.org/10.1016/j.job.2021.07.006CrossRefPubMed

14.

Biguetti CC, De Oliva AH, Healy K et al (2019) Medication-related osteonecrosis of the jaws after tooth extraction in senescent female mice treated with zoledronic acid: microtomographic, histological and immunohistochemical characterization. PLoS ONE 14:1–22. https://doi.org/10.1371/journal.pone.0214173CrossRef

15.

Liu Y, Li Z, Arioka M et al (2019) WNT3A accelerates delayed alveolar bone repair in ovariectomized mice. Osteoporos Int 30:1873–1885. https://doi.org/10.1007/s00198-019-05071-xCrossRefPubMedPubMedCentral

16.

Pereira MC, Zecchin KG, Campagnoli EB, Jorge J (2007) Ovariectomy delays alveolar wound healing after molar extractions in rats. J Oral Maxillofac Surg 65:2248–2253. https://doi.org/10.1016/j.joms.2006.11.040CrossRefPubMed

17.

Gilsanz V, Skaggs DL, Kovanlikaya A et al (1998) Differential effect of race on the axial and appendicular skeletons of children. J Clin Endocrinol Metab 83:1420–1427. https://doi.org/10.1210/jc.83.5.1420CrossRefPubMed

18.

Halloran BP, Ferguson VL, Simske SJ et al (2002) Changes in bone structure and mass with advancing age in the male C57BL/6J mouse. J Bone Miner Res 17:1044–1050. https://doi.org/10.1359/jbmr.2002.17.6.1044CrossRefPubMed

19.

Glatt V, Canalis E, Stadmeyer L, Bouxsein ML (2007) Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Miner Res 22:1197–1207. https://doi.org/10.1359/jbmr.070507CrossRefPubMed

20.

Bin YuS, Wang MQ, Li YQ et al (2009) The effects of age and sex on the expression of oestrogen and its receptors in rat mandibular condylar cartilages. Arch Oral Biol 54:479–485. https://doi.org/10.1016/j.archoralbio.2009.01.018CrossRef

21.

Mekada K, Abe K, Murakami A et al (2009) Genetic differences among C57BL/6 substrains. Exp Anim 58:141–149. https://doi.org/10.1538/expanim.58.141CrossRefPubMed

22.

Sabsovich I, Clark JD, Liao G et al (2008) Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan. Bone 42:439–451. https://doi.org/10.1016/j.bone.2007.09.041CrossRefPubMed

23.

Canderelli R, Leccesse LA, Miller NL (2007) Benefits of hormone replacement therapy in postmenopausal women. J Am Acad Nurse Pract 19:635–641. https://doi.org/10.1111/j.1745-7599.2007.00269.xCrossRefPubMed

24.

Biguetti CC, Vieira AE, Cavalla F et al (2018) CCR2 contributes to F4/80+ cells migration along intramembranous bone healing in maxilla, but its deficiency does not critically affect the healing outcome. Front Immunol. https://doi.org/10.3389/fimmu.2018.01804CrossRefPubMedPubMedCentral

25.

Hsieh YD, Devlin H, McCord F (1995) The effect of ovariectomy on the healing tooth socket of the rat. Arch Oral Biol 40:529–531. https://doi.org/10.1016/0003-9969(94)00197-JCrossRefPubMed

26.

Arioka M, Zhang X, Li Z et al (2019) Osteoporotic changes in the periodontium impair alveolar bone healing. J Dent Res 98:450–458. https://doi.org/10.1177/0022034518818456CrossRefPubMedPubMedCentral

27.

Majumdar S, Genant HK, Grampp S et al (1997) Correlation of trabecular bone structure with age, bone mineral density, and osteoporotic status: in vivo studies in the distal radius using high resolution magnetic resonance imaging. J Bone Miner Res 12:111–118. https://doi.org/10.1359/jbmr.1997.12.1.111CrossRefPubMed

28.

Vanderschueren D, Laurent MR, Claessens F et al (2014) Sex steroid actions in male bone. Endocr Rev 35:906–960. https://doi.org/10.1210/er.2014-1024CrossRefPubMedPubMedCentral

29.

Negri M, Galli C, Smerieri A, Macaluso GM, Manfredi E, Ghiacci G, Toffoli A, Bonanini M, Lumetti S (2014) The effect of age, gender, and insertion site on marginal bone loss around endosseous implants: results from a 3-year trial with premium implant system. Biomed Res Int 2014:369051. https://doi.org/10.1155/2014/369051

30.

Hassumi JS, Mulinari-Santos G, Fabris ALS et al (2018) Alveolar bone healing in rats: micro-CT, immunohistochemical and molecular analysis. J Appl Oral Sci 26:1–12. https://doi.org/10.1590/1678-7757-2017-0326CrossRef

31.

Omi M, Mishina Y (2022) Roles of osteoclasts in alveolar bone remodeling. Genes (United States) 60:1–18. https://doi.org/10.1002/dvg.23490CrossRef

32.

Assenza B, Scarano A, Petrone G et al (2003) Osteoclast activity around loaded and unloaded implants: a histological study in the beagle dog. J Oral Implantol 29:1–7. https://doi.org/10.1563/1548-1336(2003)029%3c0001:OAALAU%3e2.3.CO;2CrossRefPubMed

33.

Omi M, Mishina Y (2021) Role of osteoclasts in oral homeostasis and jawbone diseases. Oral Sci Int 18:14–27. https://doi.org/10.1002/osi2.1078CrossRef

34.

Arai F, Miyamoto T, Ohneda O et al (1999) Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor κB (RANK) receptors. J Exp Med 190:1741–1754. https://doi.org/10.1084/jem.190.12.1741CrossRefPubMedPubMedCentral

35.

Ervolino E, Statkievicz C, Toro LF et al (2019) Antimicrobial photodynamic therapy improves the alveolar repair process and prevents the occurrence of osteonecrosis of the jaws after tooth extraction in senile rats treated with zoledronate. Bone 120:101–113. https://doi.org/10.1016/j.bone.2018.10.014CrossRefPubMed

36.

Aljohani H, Senbanjo LT, Al Qranei M et al (2021) Methylsulfonylmethane increases the alveolar bone density of mandibles in aging female mice. Front Physiol 12:1–12. https://doi.org/10.3389/fphys.2021.708905CrossRef

37.

Simionato GB, da Silva ACR, Oliva AH, de Abreu Furquim EM, Couto MCR, Shinohara AL, Biguetti CC, Matsumoto MA (2021) Lack of 5-lipoxygenase in intramembranous and endochondral 129Sv mice skeleton and intramembranous healing. Arch Oral Biol 131:105266. https://doi.org/10.1016/j.archoralbio.2021.105266

38.

Marquez Hernandez RA, Ohtani J, Fujita T et al (2011) Sex hormones receptors play a crucial role in the control of femoral and mandibular growth in newborn mice. Eur J Orthod 33:564–569. https://doi.org/10.1093/ejo/cjq124CrossRefPubMed

39.

Bryda EC (2013) The Mighty Mouse: the impact of rodents on advances in biomedical research. Mo Med 110(3):207–211PubMedPubMedCentral

40.

Aguirre JI, Castillo EJ, Kimmel DB (2021) Preclinical models of medication-related osteonecrosis of the jaw (MRONJ). Bone 153:116184. https://doi.org/10.1016/j.bone.2021.116184CrossRefPubMedPubMedCentral

41.

Ko KI, Sculean A, Graves DT (2021) Diabetic wound healing in soft and hard oral tissues. Transl Res 236:72–86. https://doi.org/10.1016/j.trsl.2021.05.001CrossRefPubMedPubMedCentral

42.

Alshoiby MM, Fawzy El-Sayed KM, Elbattawy W, Hosny MM (2023) Injectable platelet-rich fibrin with demineralized freeze-dried bone allograft compared to demineralized freeze-dried bone allograft in intrabony defects of patients with stage-III periodontitis: a randomized controlled clinical trial. Clin Oral Investig. https://doi.org/10.1007/s00784-023-04954-yCrossRefPubMedPubMedCentral

43.

Grygorieva NV, Povoroznyuk VV, Gopkalova IV, Orlyk TV (2017) AGE AND SEX FEATURES OF BONE MINERAL DENSITY IN RATS. Fiziol Zh 63:26–32. https://doi.org/10.15407/fz63.01.026CrossRef

44.

Vieira AE, Repeke CE, De Barros FS et al (2015) Intramembranous bone healing process subsequent to tooth extraction in mice: Micro-computed tomography, histomorphometric and molecular characterization. PLoS ONE 10:1–22. https://doi.org/10.1371/journal.pone.0128021CrossRef

45.

Chen CH, Pei X, Tulu US et al (2018) A comparative assessment of implant site viability in humans and rats. J Dent Res 97:451–459. https://doi.org/10.1177/0022034517742631CrossRefPubMed

46.

Chen C-H, Wang L, Serdar Tulu U et al (2018) An osteopenic/osteoporotic phenotype delays alveolar bone repair. Bone 112:212–219. https://doi.org/10.1016/j.bone.2018.04.019CrossRefPubMed

47.

Manolagas SC (2010) From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev 31:266–300. https://doi.org/10.1210/er.2009-0024CrossRefPubMedPubMedCentral

48.

Garnero P, Ferreras M, Karsdal MA et al (2003) The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation. J Bone Miner Res 18:859–867. https://doi.org/10.1359/jbmr.2003.18.5.859CrossRefPubMed

49.

Delaissé JM, Engsig MT, Everts V et al (2000) Proteinases in bone resorption: obvious and less obvious roles. Clin Chim Acta 291:223–234. https://doi.org/10.1016/S0009-8981(99)00230-2CrossRefPubMed

Title: Influence of age and gender on alveolar bone healing post tooth extraction in 129 Sv mice: a microtomographic, histological, and biochemical characterization
Authors: Claudia Cristina Biguetti
Bhuvana Lakkasetter Chandrashekar
Gustavo Baroni Simionato
Nataira Regina Momesso
Marco Antonio Hungaro Duarte
Danieli C. Rodrigues
Mariza Akemi Matsumoto
Publication date: 01-06-2023
Publisher: Springer Berlin Heidelberg
Keywords: Tooth Extraction
Tooth Extraction
Published in: Clinical Oral Investigations / Issue 8/2023
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-023-05087-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Influence of age and gender on alveolar bone healing post tooth extraction in 129 Sv mice: a microtomographic, histological, and biochemical characterization

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

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