Elimination of BMP7 from the developing limb mesenchyme leads to articular cartilage degeneration and synovial inflammation with increased age

FEBS Lett. 2015 May 8;589(11):1240-8. doi: 10.1016/j.febslet.2015.04.004. Epub 2015 Apr 15.

Abstract

While osteo- and chondro-inductive activities of recombinant human bone morphogenetic protein 7 are well established, evaluation of the role of endogenous BMP7 in skeletal homeostasis has been hampered by perinatal lethality in BMP7 knockout mice. Here, we examined physiological roles of endogenous BMP7 in joint homeostasis and showed that proteoglycan contents in articular cartilage were significantly reduced in the absence of BMP7. Loss of BMP7 did not affect survival of articular cartilage cells, but resulted in reduced expression of aggrecan and enhanced expression of matrix metalloproteinase 13. We also found extensive synovial hyperplasia and enhanced expression of Activin A. These findings suggest that locally produced BMP7 is prerequisite for postnatal synovial joint homeostasis and may be involved in osteoarthritic changes in adults.

Keywords: Activin A; Articular cartilage; Bone morphogenetic protein 7; Osteoarthritis; Proteoglycan; Synovitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / biosynthesis
  • Activins / genetics
  • Adult
  • Aggrecans / biosynthesis
  • Aggrecans / genetics
  • Animals
  • Bone Morphogenetic Protein 7 / biosynthesis*
  • Bone Morphogenetic Protein 7 / genetics
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Gene Expression Regulation*
  • Hindlimb / embryology
  • Hindlimb / pathology
  • Humans
  • Mesoderm / metabolism*
  • Mesoderm / pathology
  • Mice
  • Mice, Knockout
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Synovitis / genetics
  • Synovitis / metabolism*
  • Synovitis / pathology

Substances

  • Aggrecans
  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • activin A
  • bmp7 protein, mouse
  • Activins