Destabilisation of the medial meniscus: imaging and mechanics of a murine surgical osteoarthritis model
Author(s)
Moodie, Jonathan
Type
Thesis or dissertation
Abstract
Destabilisation of the medial meniscus (DMM) is a murine surgical instability model of osteoarthritis
(OA). In this thesis the bone and cartilage changes were examined at different time points and in
different strains of mice in the DMM model.
In the first study C57Bl/6 mice underwent DMM surgery and were culled four and eight weeks postoperatively.
Tibiae were examined using confocal scanning laser microscopy (CSLM) for cartilage
changes and micro-computed tomography (micro-CT) for bone changes. Additional mice underwent
laxity testing. The tibia exhibited significant loss of cartilage and bone on the posterior plateau. A
significant increase of anterior-posterior laxity suggested that damage of the anterior cruciate
ligament had occurred during surgery, which permitted the femur to relocate to posterior tibia
causing bone and cartilage damage.
A second study investigated early stage bone changes in the DMM model. CSLM and micro-CT were
used in conjunction with non-decalcified histology. Mice received calcein injections three and six
days prior to sacrifice, and were culled two weeks after surgery. There was an increase of epiphyseal
bone volume. No change in cartilage was observed with CSLM. A significant increase of mineralising
surface/bone surface and osteoid surface/bone surface occurred at two weeks.
A final study compared the bone response of two mice strains (BALB/c and C57Bl/6). Laxity was
compared between strains eight weeks post operatively. Epiphyseal bone increased in both strains,
more so in the BALB/c which had initially less epiphyseal bone volume. There was no change in
histological mineralisation parameters or laxity measures.
In this work multi-modal imaging techniques were developed to determine the change in bone and
cartilage in the DMM model.
(OA). In this thesis the bone and cartilage changes were examined at different time points and in
different strains of mice in the DMM model.
In the first study C57Bl/6 mice underwent DMM surgery and were culled four and eight weeks postoperatively.
Tibiae were examined using confocal scanning laser microscopy (CSLM) for cartilage
changes and micro-computed tomography (micro-CT) for bone changes. Additional mice underwent
laxity testing. The tibia exhibited significant loss of cartilage and bone on the posterior plateau. A
significant increase of anterior-posterior laxity suggested that damage of the anterior cruciate
ligament had occurred during surgery, which permitted the femur to relocate to posterior tibia
causing bone and cartilage damage.
A second study investigated early stage bone changes in the DMM model. CSLM and micro-CT were
used in conjunction with non-decalcified histology. Mice received calcein injections three and six
days prior to sacrifice, and were culled two weeks after surgery. There was an increase of epiphyseal
bone volume. No change in cartilage was observed with CSLM. A significant increase of mineralising
surface/bone surface and osteoid surface/bone surface occurred at two weeks.
A final study compared the bone response of two mice strains (BALB/c and C57Bl/6). Laxity was
compared between strains eight weeks post operatively. Epiphyseal bone increased in both strains,
more so in the BALB/c which had initially less epiphyseal bone volume. There was no change in
histological mineralisation parameters or laxity measures.
In this work multi-modal imaging techniques were developed to determine the change in bone and
cartilage in the DMM model.
Date Issued
2011-08
Date Awarded
2012-04
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Shefelbine, Sandra
Sponsor
Engineering and Physical Sciences Research Council ; Smith & Nephew (Firm)
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)