Temporal pattern of gene expression and histology of stress fracture healing

Kidd, L. J., Stephens, A. S., Kuliwaba, J. S., Fazzalari, N. L., Wu, A. C. and Forwood, M. R. (2010) Temporal pattern of gene expression and histology of stress fracture healing. Bone, 46 2: 369-378. doi:10.1016/j.bone.2009.10.009

Author Kidd, L. J.
Stephens, A. S.
Kuliwaba, J. S.
Fazzalari, N. L.
Wu, A. C.
Forwood, M. R.
Title Temporal pattern of gene expression and histology of stress fracture healing
Journal name Bone   Check publisher's open access policy
ISSN 8756-3282
Publication date 2010-02
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.bone.2009.10.009
Volume 46
Issue 2
Start page 369
End page 378
Total pages 10
Editor Roland Baron
Place of publication Washington, United States
Publisher Elsevier
Collection year 2010
Language eng
Subject C1
920116 Skeletal System and Disorders (incl. Arthritis)
110314 Orthopaedics
110306 Endocrinology
110601 Biomechanics
Abstract Loading of the rat ulna is an ideal model to examine stress fracture healing. The aim of this study was to undertake a detailed examination of the histology, histomorphometry and gene expression of the healing and remodelling process initiated by fatigue-loading of the rat ulna. Ulnae were harvested 1, 2, 4, 6, 8 and 10 weeks following creation of a stress fracture. Fracture healing involved direct remodelling that progressed along the fracture line as well as woven bone proliferation at the site of the fracture. Histomorphometry demonstrated rapid progression of basic multicellular units from 1-4 weeks with significant slowing down of healing by 10 weeks after loading. Quantitative PCR was performed at 4 hours, 24 hours, 4 days, 7 days and 14 days after loading. Gene expression was compared to an unloaded control group. At 4 hours after fracture there was a marked, 220-fold increase (P<0.0001) in expression of IL-6. There were also prominent peak increases in mRNA expression for OPG, COX-2, and VEGF (all P<0.0001). At 24 hours there was a peak increase in mRNA expression for IL-11 (73-fold increase, P<0.0001). At 4 days there was a significant increase in mRNA expression for Bcl-2, COX-1, IGF-1, OPN, and SDF-1. At 7 days there was significantly increased mRNA expression of RANKL and OPN. Prominent, up-regulation of COX-2, VEGF, OPG, SDF-1, BMP-2 and SOST prior to peak expression of RANK-L indicates the importance of these factors in mediating directed remodelling of the fracture line. Dramatic, early up-regulation of IL-6 and IL-11 demonstrate their central role in initiating signalling events for remodelling and stress fracture healing.
Keyword Stress fractures
Gene expression
Bone remodelling
Q-Index Code C1
Q-Index Status Confirmed Code

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 35 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 38 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 27 Oct 2009, 11:21:45 EST by Cameron Harris on behalf of Faculty Of Nat Resources, Agric & Veterinary Sc