Matrix metalloproteinase-13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance

Simon Y. Tang, Ralf Peter Herber, Sunita P. Ho, Tamara Alliston

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Like bone mass, bone quality is specified in development, actively maintained postnatally, and disrupted by disease. The roles of osteoblasts, osteoclasts, and osteocytes in the regulation of bone mass are increasingly well defined. However, the cellular and molecular mechanisms by which bone quality is regulated remain unclear. Proteins that remodel bone extracellular matrix, such as the collagen-degrading matrix metalloproteinase (MMP)-13, are likely candidates to regulate bone quality. Using MMP-13-deficient mice, we examined the role of MMP-13 in the remodeling and maintenance of bone matrix and subsequent fracture resistance. Throughout the diaphysis of MMP-13-deficient tibiae, we observed elevated nonenzymatic cross-linking and concentric regions of hypermineralization, collagen disorganization, and canalicular malformation. These defects localize to the same mid-cortical bone regions where osteocyte lacunae and canaliculi exhibit MMP-13 and tartrate-resistant acid phosphatase (TRAP) expression, as well as the osteocyte marker sclerostin. Despite otherwise normal measures of osteoclast and osteoblast function, dynamic histomorphometry revealed that remodeling of osteocyte lacunae is impaired in MMP-13 -/- bone. Analysis of MMP-13-/- mice and their wild-type littermates in normal and lactating conditions showed that MMP-13 is not only required for lactation-induced osteocyte perilacunar remodeling, but also for the maintenance of bone quality. The loss of MMP-13, and the resulting defects in perilacunar remodeling and matrix organization, compromise MMP-13 -/- bone fracture toughness and postyield behavior. Taken together, these findings demonstrate that osteocyte perilacunar remodeling of mid-cortical bone matrix requires MMP-13 and is essential for the maintenance of bone quality.

Original languageEnglish
Pages (from-to)1936-1950
Number of pages15
JournalJournal of Bone and Mineral Research
Volume27
Issue number9
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Keywords

  • BONE MATRIX
  • BONE QUALITY
  • FRACTURE RESISTANCE
  • MATRIX METALLOPROTEINASE-13
  • OSTEOCYTE
  • OSTEOCYTE PERILACUNAR REMODELING
  • REMODELING

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