Differential effects between the loss of MMP-2 and MMP-9 on structural and tissue-level properties of bone

Jeffry S. Nyman, Conor C. Lynch, Daniel S. Perrien, Sophie Thiolloy, Elizabeth C. O'Quinn, Chetan A. Patil, Xiaohong Bi, George M. Pharr, Anita Mahadevan-Jansen, Gregory R. Mundy

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1252-1260
Number of pages9
JournalJournal of Bone and Mineral Research
Issue number6
StatePublished - Jun 2011
Externally publishedYes


  • Collagen
  • Matrix Metalloproteinase
  • MCT
  • Mineral
  • Nanoindentation
  • Raman

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine


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