9 research outputs found
Over-expression of amyloid precursor protein in HEK cells alters p53 conformational state and protects against doxorubicin
Estimation of Size and Shape of Pores in Moist Coal Utilizing Sorbed Water as a Molecular Probe
Development of an Integrated Surface Stimulation Device for Systematic Evaluation of Wound Electrotherapy
Costimulatory Effects of Interferon-γ and Interleukin-1β or Tumor Necrosis Factor α on the Synthesis of Aβ1-40 and Aβ1-42 by Human Astrocytes
Cathepsin K Activity-dependent Regulation of Osteoclast Actin Ring Formation and Bone Resorption*
Cathepsin K is responsible for the degradation of type I collagen in
osteoclast-mediated bone resorption. Collagen fragments are known to be
biologically active in a number of cell types. Here, we investigate their
potential to regulate osteoclast activity. Mature murine osteoclasts were
seeded on type I collagen for actin ring assays or dentine discs for
resorption assays. Cells were treated with cathepsins K-, L-, or
MMP-1-predigested type I collagen or soluble bone fragments for 24 h. The
presence of actin rings was determined fluorescently by staining for actin. We
found that the percentage of osteoclasts displaying actin rings and the area
of resorbed dentine decreased significantly on addition of cathepsin
K-digested type I collagen or bone fragments, but not with cathepsin L or
MMP-1 digests. Counterintuitively, actin ring formation was found to decrease
in the presence of the cysteine proteinase inhibitor LHVS and in cathepsin
K-deficient osteoclasts. However, cathepsin L deficiency or the general MMP
inhibitor GM6001 had no effect on the presence of actin rings. Predigestion of
the collagen matrix with cathepsin K, but not by cathepsin L or MMP-1 resulted
in an increased actin ring presence in cathepsin K-deficient osteoclasts.
These studies suggest that cathepsin K interaction with type I collagen is
required for 1) the release of cryptic Arg-Gly-Asp motifs during the initial
attachment of osteoclasts and 2) termination of resorption via the creation of
autocrine signals originating from type I collagen degradation