Increased Runx2 Expression Associated with Enhanced Wnt Signaling in PDLLA Internal Fixation for Fracture Treatment

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2017 Jun 2

PMID 28565812

Citations 5

Authors

Zhuoyan Ling

Lei Wu

Gaolong Shi

Li Chen

Qirong Dong

Affiliations

Soon will be listed here.

Abstract

Poly-D-L lactide (PDLLA) biodegradable implants to heal fractures are widely applied in orthopedic surgeries. However, whether the process of fracture healing is regulated differently when PDLLA is used compared with traditional metal materials remains unclear. Runt-related transcription factor 2 (Runx2) and canonical Wnt signaling are essential and may interact reciprocally in the regulation of osteogenesis during bone repair. In the present study, a rat femoral open osteotomy model was used to compare the curative efficacy of a PDLLA rod and Kirschner wire under intramedullary fixation for fracture treatment. The dynamic expression of Runx2 and key components of the canonical Wnt signaling in callus tissue during fracture healing was also investigated. The results of the current study indicate that at weeks 4 and 6 following fixation, the callus bone structural parameters of microCT were significantly improved by PDLLA rod compared to that of Kirschner wire. In addition, at weeks 4 and 6 after fixation, the protein and mRNA expression of Runx2 and the positive regulators of canonical Wnt signaling, such as Wnts and β-catenin, were significantly increased. However, the protein and mRNA expression levels of the negative regulators of canonical Wnt signaling, such as glycogen synthase kinase-3β, were significantly decreased in callus tissue when treated with PDLLA rod compared with Kirschner wire. Collectively, these data indicate that compared to the traditional metal material, using PDLLA internal fixation for fracture treatment may further improve bone formation, which is associated with the increased expression of Runx2 and the enhancement of canonical Wnt signaling.

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References

Waris E, Ashammakhi N, Raatikainen T, Tormala P, Santavirta S, Konttinen Y . Self-reinforced bioabsorbable versus metallic fixation systems for metacarpal and phalangeal fractures: a biomechanical study. J Hand Surg Am. 2002; 27(5):902-9. DOI: 10.1053/jhsu.2002.35082. View

Yonden Z, Aydin M, Alcin E, Kelestemur M, Kutlu S, Yilmaz B . Effects of letrozole on bone biomarkers and femur fracture in female rats. J Physiol Biochem. 2010; 65(3):267-75. DOI: 10.1007/BF03180579. View

Chen Y, Whetstone H, Lin A, Nadesan P, Wei Q, Poon R . Beta-catenin signaling plays a disparate role in different phases of fracture repair: implications for therapy to improve bone healing. PLoS Med. 2007; 4(7):e249. PMC: 1950214. DOI: 10.1371/journal.pmed.0040249. View

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K . Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997; 89(5):755-64. DOI: 10.1016/s0092-8674(00)80258-5. View

Fahrleitner-Pammer A, Dobnig H, Piswanger-Soelkner C, Bonelli C, Dimai H, Leb G . Osteoprotegerin serum levels in women: correlation with age, bone mass, bone turnover and fracture status. Wien Klin Wochenschr. 2003; 115(9):291-7. DOI: 10.1007/BF03040334. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Waris E, Ashammakhi N, Kaarela O, Raatikainen T, Vasenius J . Use of bioabsorbable osteofixation devices in the hand. J Hand Surg Br. 2004; 29(6):590-8. DOI: 10.1016/j.jhsb.2004.02.005. View

Eastman Q, Grosschedl R . Regulation of LEF-1/TCF transcription factors by Wnt and other signals. Curr Opin Cell Biol. 1999; 11(2):233-40. DOI: 10.1016/s0955-0674(99)80031-3. View

Heidemann W, Jeschkeit S, Ruffieux K, Fischer J, Wagner M, Kruger G . Degradation of poly(D,L)lactide implants with or without addition of calciumphosphates in vivo. Biomaterials. 2001; 22(17):2371-81. DOI: 10.1016/s0142-9612(00)00424-5. View

10.

Xu H, Duan J, Ning D, Li J, Liu R, Yang R . Role of Wnt signaling in fracture healing. BMB Rep. 2014; 47(12):666-72. PMC: 4345510. DOI: 10.5483/bmbrep.2014.47.12.193. View

11.

Rennert J, Coffman J, Mushegian A, Robertson A . The evolution of Runx genes I. A comparative study of sequences from phylogenetically diverse model organisms. BMC Evol Biol. 2003; 3:4. PMC: 153517. DOI: 10.1186/1471-2148-3-4. View

12.

Claes L, Recknagel S, Ignatius A . Fracture healing under healthy and inflammatory conditions. Nat Rev Rheumatol. 2012; 8(3):133-43. DOI: 10.1038/nrrheum.2012.1. View

13.

Carroll S, Ravid K . Differentiation of mesenchymal stem cells to osteoblasts and chondrocytes: a focus on adenosine receptors. Expert Rev Mol Med. 2013; 15:e1. DOI: 10.1017/erm.2013.2. View

14.

Yee C, Xie L, Hatsell S, Hum N, Murugesh D, Economides A . Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model. Bone. 2015; 82:122-34. PMC: 4635060. DOI: 10.1016/j.bone.2015.04.048. View

15.

Rosier R, OKeefe R, Hicks D . The potential role of transforming growth factor beta in fracture healing. Clin Orthop Relat Res. 1999; (355 Suppl):S294-300. DOI: 10.1097/00003086-199810001-00030. View

16.

Jansen J, Koopmans S, Los L, Van der Worp R, Podt J, Hooymans J . Intraocular degradation behavior of crosslinked and linear poly(trimethylene carbonate) and poly(D,L-lactic acid). Biomaterials. 2011; 32(22):4994-5002. DOI: 10.1016/j.biomaterials.2011.03.062. View

17.

Bustamante M, Nogues X, Agueda L, Jurado S, Wesselius A, Caceres E . Promoter 2 -1025 T/C polymorphism in the RUNX2 gene is associated with femoral neck bmd in Spanish postmenopausal women. Calcif Tissue Int. 2007; 81(4):327-32. DOI: 10.1007/s00223-007-9069-2. View

18.

Rokkanen P, Bostman O, Vainionpaa S, Vihtonen K, Tormala P, Laiho J . Biodegradable implants in fracture fixation: early results of treatment of fractures of the ankle. Lancet. 1985; 1(8443):1422-4. DOI: 10.1016/s0140-6736(85)91847-1. View

19.

Harada H, Tagashira S, Fujiwara M, Ogawa S, Katsumata T, Yamaguchi A . Cbfa1 isoforms exert functional differences in osteoblast differentiation. J Biol Chem. 1999; 274(11):6972-8. DOI: 10.1074/jbc.274.11.6972. View

20.

Ueta C, Iwamoto M, Kanatani N, Yoshida C, Liu Y, Enomoto-Iwamoto M . Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes. J Cell Biol. 2001; 153(1):87-100. PMC: 2185519. DOI: 10.1083/jcb.153.1.87. View