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2016 ; 52-54
(ä): 141-150
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English Wikipedia
Biglycan potentially regulates angiogenesis during fracture repair by altering
expression and function of endostatin
#MMPMID27072616
Myren M
; Kirby DJ
; Noonan ML
; Maeda A
; Owens RT
; Ricard-Blum S
; Kram V
; Kilts TM
; Young MF
Matrix Biol
2016[May]; 52-54
(ä): 141-150
PMID27072616
show ga
The small proteoglycan biglycan (Bgn) is highly expressed in the organic matrix
of bone and plays a role in bone formation. Previous work implicated Bgn in
vessel growth during bone healing [1]. By infusing barium sulfate (BaSO4) into WT
and Bgn-deficient mice we discovered the positive effect of Bgn in modulating
angiogenesis during fracture healing. Using micro-computed tomography angiography
we found significant differences in the vessel size and volume among other
parameters. To further understand the mechanistic basis for this, we explored the
relationship between Bgn and the anti-angiogenic protein endostatin.
Immunohistochemistry (IHC) showed co-localization of Bgn and endostatin in
regions of bone formation, with increased endostatin staining in Bgn-KO compared
to WT at 14days post-fracture. To further elucidate the relationship between Bgn
and endostatin, an endothelial cell tube formation assay was used. This study
showed that endothelial cells treated with endostatin had significantly decreased
vessel length and vessel branches compared to untreated cells, while cells
treated with endostatin and Bgn at a 1:1M ratio had vessel length and vessel
branches comparable to untreated cells. This indicated that Bgn was able to
mitigate the inhibitory effect of endostatin on endothelial cell growth. In
summary, these results suggest that Bgn is needed for proper blood vessel
formation during fracture healing, and one mechanism by which Bgn impacts
angiogenesis is through inhibition of endostatin.