Summary
Objective
Osteoarthritis (OA) has recently been suggested to be associated with diabetes. However,
this association often disappears when accounting for body mass index (BMI), suggesting
that mechanical stress may be a confounding factor. We investigated the combined influence
of glucose level and loading stress on OA progression using a novel whole joint-in-motion
(JM) culture system.
Design
Whole mouse knee joints were placed in an enclosed chamber with culture media and
actuated to recapitulate leg movement, with a dynamic stress regimen of 0.5 Hz, 8 h/day
for 7 days. These joints were treated with varying levels of glucose and controlled
for osmolarity and diffusion. Joint movement and joint space were examined by X-ray
fluoroscopy and microCT. Cartilage matrix levels were quantified by blinded Mankin
scoring and immunohistochemistry.
Results
Culturing in the JM device facilitated proper leg extension and flexion movements,
and adequate mass transport for analyzing the effect of glucose on cartilage. Treatment
with higher levels of glucose either via media supplementation or intra-articular
injection caused a significant decrease in levels of glycosaminoglycan (GAG) and an
increase in aggrecan neoepitope in articular cartilage, but only under dynamic stress.
Additionally, collagen II level was slightly reduced by high glucose levels.
Conclusions
High levels of glucose and dynamic stress have permissive effects on articular cartilage
GAG loss and aggrecan degradation, implicating that mechanical stress confounds the
association of diabetes with OA. The JM device supports novel investigation of mechanical
stress on the integrity of an intact living mouse joint to provide insights into OA
pathogenesis.
Keywords
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Article info
Publication history
Published online: November 11, 2022
Accepted:
October 13,
2022
Received:
February 9,
2022
Identification
Copyright
© 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
