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2015 ; 10
(12
): e0144541
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Medicarpin, a Natural Pterocarpan, Heals Cortical Bone Defect by Activation of
Notch and Wnt Canonical Signaling Pathways
#MMPMID26657206
Dixit M
; Raghuvanshi A
; Gupta CP
; Kureel J
; Mansoori MN
; Shukla P
; John AA
; Singh K
; Purohit D
; Awasthi P
; Singh D
; Goel A
PLoS One
2015[]; 10
(12
): e0144541
PMID26657206
show ga
We evaluated the bone regeneration and healing effect of Medicarpin (med) in
cortical bone defect model that heals by intramembranous ossification. For the
study, female Sprague-Dawley rats were ovariectomized and rendered osteopenic. A
drill hole injury was generated in mid femoral bones of all the animals. Med
treatment was commenced the day after and continued for 15 days. PTH was taken as
a reference standard. Fifteen days post-treatment, animals were sacrificed. Bones
were collected for histomorphometry studies at the injury site by micro-computed
tomography (?CT) and confocal microscopy. RNA and protein was harvested from
newly generated bone. For immunohistochemistry, 5?m sections of decalcified femur
bone adjoining the drill hole site were cut. By ?CT analysis and calcein labeling
of newly generated bone it was found that med promotes bone healing and new bone
formation at the injury site and was comparable to PTH in many aspects. Med
treatment led to increase in the Runx-2 and osteocalcin signals indicating
expansion of osteoprogenitors at the injury site as evaluated by qPCR and
immunohistochemical localization. It was observed that med promoted bone
regeneration by activating canonical Wnt and notch signaling pathway. This was
evident by increased transcript and protein levels of Wnt and notch signaling
components in the defect region. Finally, we confirmed that med treatment leads
to elevated bone healing in pre-osteoblasts by co localization of beta catenin
with osteoblast marker alkaline phosphatase. In conclusion, med treatment
promotes new bone regeneration and healing at the injury site by activating
Wnt/canonical and notch signaling pathways. This study also forms a strong case
for evaluation of med in delayed union and non-union fracture cases.
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