Premium
Differential regulation of blood vessel formation between standard and delayed bone healing
Author(s) -
Lienau Jasmin,
SchmidtBleek Katharina,
Peters Anja,
Haschke Franek,
Duda Georg N.,
Perka Carsten,
Bail Hermann J.,
Schütze Norbert,
Jakob Franz,
Schell Hanna
Publication year - 2009
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20870
Subject(s) - bone healing , blood vessel , osteotomy , wound healing , callus , medicine , cord blood , angiogenesis , pathology , anatomy , andrology , surgery , biology , genetics
Blood vessel formation is a prerequisite for bone healing. In this study, we tested the hypothesis that a delay in bone healing is associated with an altered regulation of blood vessel formation. A tibial osteotomy was performed in two groups of sheep and stabilized with either a rigid external fixator leading to standard healing or with a highly rotationally unstable one leading to delayed healing. At days 4, 7, 9, 11, 14, 21, and 42 after surgery, total RNA was extracted from the callus. Gene expressions of vWF , an endothelial cell marker, and of several molecules related to blood vessel formation were studied by qPCR. Furthermore, histology was performed on fracture hematoma and callus sections. Histologically, the first blood vessels were detected at day 7 in both groups. mRNA expression levels of vWF , Ang1 , Ang2 , VEGF , CYR61 , FGF2 , MMP2 , and TIMP1 were distinctly lower in the delayed compared to the standard healing group at several time points. Based on differential expression patterns, days 7 and 21 postoperatively were revealed to be essential time points for vascularization of the ovine fracture callus. This work demonstrates for the first time a differential regulation of blood vessel formation between standard and mechanically induced delayed healing in a sheep osteotomy model. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res