Differential effects between the loss of MMP-2 and MMP-9 on structural and tissue-level properties of bone
Open Access
- 29 December 2010
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 26 (6), 1252-1260
- https://doi.org/10.1002/jbmr.326
Abstract
Matrix metalloproteinases (MMPs) are capable of processing certain components of bone tissue, including type 1 collagen, a determinant of the biomechanical properties of bone tissue, and they are expressed by osteoclasts and osteoblasts. Therefore, we posit that MMP activity can affect the ability of bone to resist fracture. To explore this possibility, we determined the architectural, compositional, and biomechanical properties of bones from wild‐type (WT), Mmp2−/−, and Mmp9−/− female mice at 16 weeks of age. MMP‐2 and MMP‐9 have similar substrates but are expressed primarily by osteoblasts and osteoclasts, respectively. Analysis of the trabecular compartment of the tibia metaphysis by micro–computed tomography (µCT) revealed that these MMPs influence trabecular architecture, not volume. Interestingly, the loss of MMP‐9 improved the connectivity density of the trabeculae, whereas the loss of MMP‐2 reduced this parameter. Similar differential effects in architecture were observed in the L5 vertebra, but bone volume fraction was lower for both Mmp2−/− and Mmp9−/− mice than for WT mice. The mineralization density and mineral‐to‐collagen ratio, as determined by µCT and Raman microspectroscopy, were lower in the Mmp2−/− bones than in WT control bones. Whole‐bone strength, as determined by three‐point bending or compression testing, and tissue‐level modulus and hardness, as determined by nanoindentation, were less for Mmp2−/− than for WT bones. In contrast, the Mmp9−/− femurs were less tough with lower postyield deflection (more brittle) than the WT femurs. Taken together, this information reveals that MMPs play a complex role in maintaining bone integrity, with the cell type that expresses the MMP likely being a contributing factor to how the enzyme affects bone quality. © 2011 American Society for Bone and Mineral Research.Keywords
This publication has 46 references indexed in Scilit:
- Raman and mechanical properties correlate at whole bone- and tissue-levels in a genetic mouse modelJournal of Biomechanics, 2011
- Clinical and radiographic findings in two brothers affected with a novel mutation in matrix metalloproteinase 2 geneEuropean Journal of Pediatrics, 2009
- TGF-β1–induced migration of bone mesenchymal stem cells couples bone resorption with formationNature Medicine, 2009
- Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on BonePLOS ONE, 2009
- Matrix metalloproteinases and boneBone, 2008
- Elevated TGF-β2 signaling in dentin results in sex related enamel defectsArchives of Oral Biology, 2007
- Loss of MMP-2 disrupts skeletal and craniofacial development and results in decreased bone mineralization, joint erosion and defects in osteoblast and osteoclast growthHuman Molecular Genetics, 2007
- The interaction of microstructure and volume fraction in predicting failure in cancellous boneBone, 2006
- (Pre-)Osteoclasts Induce Retraction of Osteoblasts Before Their Fusion to OsteoclastsJournal of Bone and Mineral Research, 2004
- Measurement of hardness and elastic modulus by instrumented indentation: Advances in understanding and refinements to methodologyJournal of Materials Research, 2004