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06:17
Osteoclast Derivation from Mouse Bone Marrow
Published on: November 6, 2014
Augmented LPS responsiveness in type 1 diabetes-derived osteoclasts
Dana L Catalfamo1, Nadia L Calderon, Scott W Harden
1Department of Periodontology, College of Dentistry, University of Florida, Gainesville, Florida 32610, USA.
Journal of Cellular Physiology
|June 22, 2012
Summary
Type 1 diabetes (T1D) osteoclasts from a mouse model show increased bone resorption due to enhanced enzyme activity and responsiveness to inflammatory signals. This suggests T1D directly impacts bone-degrading cells, contributing to skeletal abnormalities.
Area of Science:
- Immunology
- Endocrinology
- Bone Biology
Background:
- Type 1 diabetes (T1D) frequently causes bone abnormalities, impacting osteoblast and osteoclast function.
- The role of immune mediators in T1D-associated osteoclast dysfunction and bone pathology remains less understood.
Purpose of the Study:
- To characterize osteoclast differentiation and function in a mouse model of T1D.
- To investigate the influence of inflammatory mediators on T1D osteoclast activity.
Main Methods:
- Utilized bone marrow-derived osteoclasts (BM-OCs) from non-obese diabetic (NOD) mice, a model for T1D.
- Evaluated osteoclast differentiation, bone resorption, and expression of cathepsin K, MMP-9, and soluble mediators.
- Assessed BM-OC response to lipopolysaccharide (LPS) and a pro-inflammatory cytokine cocktail.
Main Results:
- NOD BM-OCs exhibited increased bone resorption despite smaller cell size, with elevated cathepsin K, MMP-9, and pro-osteoclastogenic mediator expression.
- NOD BM-OCs showed inhibited LPS-induced deactivation, independent of soluble mediators produced by the osteoclasts.
- A pro-inflammatory environment enhanced NOD BM-OC bone resorption.
Conclusions:
- Osteoclasts from T1D model mice hyper-respond to RANK-L, leading to excessive bone degradation.
- Enhanced cathepsin K and MMP-9 secretion, along with increased pro-osteoclastic mediators, contribute to bone loss in T1D.
- Inhibited LPS-induced deactivation in NOD osteoclasts is likely due to intrinsic cellular responsiveness rather than soluble mediator production.
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