Comparison of gene expression of bone regulators and bone microstructure in 20 weeks old female mice of two different strains (C57BL/6J and C3H/HeOuJ)

. 2025 Mar ; 9 (3) : ziaf004. [epub] 20250110

Status PubMed-not-MEDLINE Jazyk angličtina Země Velká Británie, Anglie Médium electronic-ecollection

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid39925624

A huge number of inbred mouse strains with different bone properties have become available for musculoskeletal research. C57Bl/6J and C3H/HeOuJ mice show a significant difference in their bone characteristics. Nevertheless, there is a lack of knowledge on the molecular basis of these strain differences. The aim of this study is to determine the gene expression of selected regulators expressed in the bone marrow as well as bone microstructure of C57Bl/6J and C3H/HeOuJ mice. Bone properties were investigated in 20-week-old female C57Bl/6J and C3H/HeOuJ mice. Total RNA was extracted from the bone marrow of the tibia and gene expression of the following genes was determined by quantitative real-time PCR: SOST, DKK1, OPN, FGF23, RANKL, IL6, TNF, IL17a, and OPG. The femur and third lumbar vertebral body (L3) were investigated by μCT. Bone histomorphometric evaluations were performed in tartrate-resistant acid phosphatase/toluidine blue stained fourth lumbar vertebral bodies (L4). C57Bl/6J and C3H/HeOuJ mice showed significant differences in the gene expression of DKK1, FGF23, IL-6, TNF, and OPG. When compared with C57Bl/6J mice, C3H/HeOuJ mice had a stronger cortical and trabecular bone microstructure at the femur. In contrast, at L3 bone volume/total volume (BV/TV) and trabecular number were significantly higher in C57Bl/6J than in C3H/HeOuJ mice. Bone histomorphometry of L4 revealed significantly higher BV/TV, trabecular number, and thickness in C57Bl/6J mice. Furthermore, the number of osteoblasts and the number of osteoclasts/bone perimeter were higher in the C57Bl/6J mice. This study shows that C57Bl/6J and C3H/HeOuJ mice exhibit a differential expression of cytokines present in the bone marrow. Bone properties differ not only between both strains but also in relation to the investigated bone region.

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Rosen  CJ, Beamer  WG  Mouse Genetics as a Tool to Study Bone Development and Physiology ;  Elsevier, 2010,  10.1016/B978-0-12-375098-3.50012-3. DOI

Chen  C, Kalu  DN. Strain differences in bone density and calcium metabolism between C3H/HEJ and C57BL/6J mice. Bone. 1999;25(4):413–420. 10.1016/S8756-3282(99)00185-4 PubMed DOI

Turner  CH, Hsieh  Y-F, Müller  R, et al.  Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice. J Bone Miner Res. 2000;15(6):1126–1131. 10.1359/jbmr.2000.15.6.1126 PubMed DOI

Voide  R, van Lenthe  GH, Müller  R. Differential effects of bone structural and material properties on bone competence in C57BL/6 and C3H/He inbred strains of mice. Calcif Tissue Int. 2008;83(1):61–69. 10.1007/s00223-008-9120-y PubMed DOI

Beamer  WG, Donahue  LR, Rosen  CJ, Baylink  DJ. Genetic variability in adult bone density among inbred strains of mice. Bone. 1996;18(5):397–403. 10.1016/8756-3282(96)00047-6 PubMed DOI

Richman  C, Kutilek  S, Miyakoshi  N, et al.  Postnatal and pubertal skeletal changes contribute predominantly to the differences in peak bone density between C3H/HeJ and C57BL/6J mice. J Bone Miner Res. 2001;16(2):386–397. 10.1359/jbmr.2001.16.2.386 PubMed DOI

Akhter  MP, Iwaniec  UT, Covey  MA, Cullen  DM, Kimmel  DB, Recker  RR. Genetic variations in bone density, histomorphometry, and strength in mice. Calcif Tissue Int. 2000;67(4):337–344. 10.1007/s002230001144 PubMed DOI

Sheng  MH-C, Baylink  DJ, Beamer  WG, et al.  Histomorphometric studies show that bone formation and bone mineral apposition rates are greater in C3H/HeJ (high-density) than C57BL/6J (low-density) mice during growth. Bone. 1999;25(4):421–429. 10.1016/S8756-3282(99)00184-2 PubMed DOI

Kodama  Y, Umemura  Y, Nagasawa  S, et al.  Exercise and mechanical loading increase periosteal bone formation and whole bone strength in C57BL/6J mice but not in C3H/HeJ mice. Calcif Tissue Int. 2000;66(4):298–306. 10.1007/s002230010060 PubMed DOI

Judex  S, Garman  R, Squire  M, Busa  B, Donahue  L-R, Rubin  C. Genetically linked site-specificity of disuse osteoporosis. J Bone Miner Res. 2004;19(4):607–613. 10.1359/JBMR.040110 PubMed DOI

Lodberg  A, Vegger  JB, Jensen  MV, Larsen  CM, Thomsen  JS, Brüel  A. Immobilization induced osteopenia is strain specific in mice. Bone Rep. 2015;2:59–67. 10.1016/j.bonr.2015.04.001 PubMed DOI PMC

Livak  KJ, Schmittgen  TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25(4):402–408. 10.1006/meth.2001.1262 PubMed DOI

Bouxsein  ML, Boyd  SK, Christiansen  BA, Guldberg  RE, Jepsen  KJ, Müller  R. Guidelines for assessment of bone microstructure in rodents using micro–computed tomography. J Bone Miner Res. 2010;25(7):1468–1486. 10.1002/jbmr.141 PubMed DOI

Kerschan-Schindl  K, Papageorgiou  M, Föger-Samwald  U, Butylina  M, Weber  M, Pietschmann  P. Assessment of bone microstructure by micro CT in C57BL/6J mice for sex-specific differentiation. IJMS. 2022;23(23):14585. 10.3390/ijms232314585 PubMed DOI PMC

Papageorgiou  M, Föger-Samwald  U, Wahl  K, Kerschan-Schindl  K, Pietschmann  P. Age- and strain-related differences in bone microstructure and body composition during development in inbred male mouse strains. Calcif Tissue Int. 2020;106(4):431–443. 10.1007/s00223-019-00652-8 PubMed DOI

Föger-Samwald  U, Knecht  C, Stimpfl  T, et al.  Bone effects of binge alcohol drinking using prepubescent pigs as a model. Alcohol Clin Exp Res. 2018;42(11):2123–2135. 10.1111/acer.13874 PubMed DOI PMC

Dempster  DW, Compston  JE, Drezner  MK, et al.  Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 2013;28(1):2–17. 10.1002/jbmr.1805 PubMed DOI PMC

Idris  A. Bone Research Protocols: Third Edition. Aymen I. Idris (Editor), Humana Press, 2019. 10.1007/978-1-4939-8997-3. DOI

Ganapamo  F, Dennis  VA, Philipp  MT. Differential acquired immune responsiveness to bacterial lipoproteins in Lyme disease-resistant and -susceptible mouse strains. Eur J Immunol. 2003;33(7):1934–1940. 10.1002/eji.200323655 PubMed DOI

Gautam  A, Dixit  S, Embers  M, et al.  Different patterns of expression and of IL-10 modulation of inflammatory mediators from macrophages of Lyme disease-resistant and -susceptible mice. PLoS One. 2012;7(9):e43860. 10.1371/journal.pone.0043860 PubMed DOI PMC

Zhang  M, Yin  L, Zhang  K, et al.  Response patterns of cytokines/chemokines in two murine strains after irradiation. Cytokine. 2012;58(2):169–177. 10.1016/j.cyto.2011.12.023 PubMed DOI

Matsutani  T, Ananthasamy  T, Kang  S, Bland  K, Chaudry  I. Mouse genetic background influences severity of immune responses following trauma-hemorrhage. Cytokine. 2005;30(4):168–176. 10.1016/j.cyto.2004.12.019 PubMed DOI

Balga  R, Wetterwald  A, Portenier  J, Dolder  S, Mueller  C, Hofstetter  W. Tumor necrosis factor-alpha: alternative role as an inhibitor of osteoclast formation in vitro. Bone. 2006;39(2):325–335. 10.1016/j.bone.2006.02.056 PubMed DOI

Kim  MY, Lee  K, Shin  H-I, Lee  K-J, Jeong  D. Metabolic activities affect femur and lumbar vertebrae remodeling, and anti-resorptive risedronate disturbs femoral cortical bone remodeling. Exp Mol Med. 2021;53(1):103–114. 10.1038/s12276-020-00548-w PubMed DOI PMC

Akhter  MP, Otero  JK, Iwaniec  UT, Cullen  DM, Haynatzki  GR, Recker  RR. Differences in vertebral structure and strength of inbred female mouse strains. J Musculoskelet Neuronal Interact. 2004;4:33–40. PubMed

Föger-Samwald  U, Papageorgiou  M, Wahl-Figlash  K, Kerschan-Schindl  K, Pietschmann  P. Bone and muscle development in three inbred female mouse strains. Osteologie. 2021;30:173–181.

Bouxsein  ML, Myers  KS, Shultz  KL, Donahue  LR, Rosen  CJ, Beamer  WG. Ovariectomy-induced bone loss varies among inbred strains of mice. J Bone Miner Res. 2005;20(7):1085–1092. 10.1359/JBMR.050307 PubMed DOI

Buie  HR, Moore  CP, Boyd  SK. Postpubertal architectural developmental patterns differ between the L3 vertebra and proximal tibia in three inbred strains of mice. J Bone Miner Res. 2020;23(12):2048–2059. 10.1359/jbmr.080808 PubMed DOI

Akhter  MP, Cullen  DM, Pedersen  EA, Kimmel  DB, Recker  RR. Bone response to in vivo mechanical loading in two breeds of mice. Calcif Tissue Int. 1998;63(5):442–449. 10.1007/s002239900554 PubMed DOI

Sheng  MH-C, Baylink  DJ, Beamer  WG, Donahue  LR, Lau  K-HW, Wergedal  JE. Regulation of bone volume is different in the metaphyses of the femur and vertebra of C3H/HeJ and C57BL/6J mice. Bone. 2002;30(3):486–491. 10.1016/S8756-3282(01)00693-7 PubMed DOI

Kaye  M, Kusy  RP. Genetic lineage, bone mass, and physical activity in mice. Bone. 1995;17(2):131–135. 10.1016/S8756-3282(00)00164-2 PubMed DOI

Bikle  DD, Harris  J, Halloran  BP, Morey-Holton  ER. Skeletal unloading induces resistance to insulin-like growth factor I. J Bone Miner Res. 1994;9(11):1789–1796. 10.1002/jbmr.5650091116 PubMed DOI

Kostenuik  PJ, Harris  J, Halloran  BP, Turner  RT, Morey-Holton  ER, Bikle  DD. Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I. J Bone Miner Res. 1999;14(1):21–31. 10.1359/jbmr.1999.14.1.21 PubMed DOI

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