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Human osteoblasts produce cathepsin K

Institute of Biomedicine/Anatomy, Biomedicum Helsinki, PO Box 63, FI-00014 University of Helsinki, Finland.
Bone (Impact Factor: 4.46). 07/2006; 38(6):769-77. DOI: 10.1016/j.bone.2005.10.017
Source: PubMed

ABSTRACT Healthy bone is a rigid yet living tissue that undergoes continuous remodeling. Osteoclasts resorb bone in the remodeling cycle. They secrete H(+)-ions and proteinases to dissolve bone mineral and degrade organic bone matrix, respectively. One of the main collagenolytic proteinase in osteoclasts is cathepsin K, a member of papain family cysteine proteinases. Recently, it has been shown that osteoblasts may contribute to organic matrix remodeling. We therefore investigated their ability to produce cathepsin K for this action. Trabecular bone samples were collected from patients operated due to a fracture of the femoral neck. Part of the bone was decalcified and the rest was used for cell isolation. Sections from the decalcified bone were immunostained with antibodies against cathepsin K. Isolated cells were characterized for their ability to form mineralized matrix and subsequently analyzed for their cathepsin K production by Western blotting and quantitative RT-PCR. Osteoblasts, bone lining cells and some osteocytes in situ showed cathepsin K immunoreactivity and osteoblast-like cells in vitro produced cathepsin K mRNA and released both 42 kDa pro- and 27 kDa processed cathepsin K to culture media. Osteoblastic cathepsin K may thus contribute to collagenous matrix maintenance and recycling of improperly processed collagen I. Whether osteoblastic cathepsin K synthesis has consequences in diseases characterized by abnormal bone matrix turnover remains to be investigated.

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    • "Cathepsin K is the major cysteine protease secreted by the osteoclasts and has been identified in intracellular vesicles, vesicles close to the ruffled border, and in resorption lacuna [12]. Cathepsin K is mainly found in osteoclasts though it is widely expressed but to a lesser extent in human ovary, heart, skeletal muscle, lung, placenta, testis, small intestine, and colon [13], and also in human osteoblasts [14]. If bone formation and bone resorption are unbalanced with excessive resorption, osteoporosis ensues, causing an increased propensity to fracture [15]. "
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    • "Cathepsin K is the major cysteine protease secreted by the osteoclasts and has been identified in intracellular vesicles, vesicles close to the ruffled border, and in resorption lacuna [12]. Cathepsin K is mainly found in osteoclasts though it is widely expressed but to a lesser extent in human ovary, heart, skeletal muscle, lung, placenta, testis, small intestine, and colon [13], and also in human osteoblasts [14]. If bone formation and bone resorption are unbalanced with excessive resorption, osteoporosis ensues, causing an increased propensity to fracture [15]. "
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    • "Cathepsin K is the major cysteine protease secreted by the osteoclasts and has been identified in intracellular vesicles, vesicles close to the ruffled border, and in resorption lacuna [12]. Cathepsin K is mainly found in osteoclasts though it is widely expressed but to a lesser extent in human ovary, heart, skeletal muscle, lung, placenta, testis, small intestine, and colon [13], and also in human osteoblasts [14]. If bone formation and bone resorption are unbalanced with excessive resorption, osteoporosis ensues, causing an increased propensity to fracture [15]. "
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    ABSTRACT: This study evaluates the effect of the mother-of-pearl (nacre) organic matrix on mammalian osteoclast activity and on cathepsin K protease. Rabbit osteoclasts were cultured on bovine cortical bone slices in the presence of water-soluble molecules extracted from nacre of the pearl oyster Pinctada margaritifera. Osteoclast resorption activity was determined by quantification of the resorption surface area on bovine bone slices. Papain and cathepsin K, B and L inhibition tests were performed in the presence of the nacre water-soluble extracts. The active crude extract was fractionated by dialysis and reversed-phase high-performance liquid chromatography before electrospray mass spectrometry analysis of inhibitory fractions. The water-soluble molecules extracted from nacre decreased bone resorption without jeopardizing osteoclast survival. The hydrolytic activity of cysteine proteinases was reduced when the enzymes were incubated with the nacre water-soluble molecules. Trending towards characterization of the molecules involved, it appears that cathepsin K inhibitors remain in different nacre water-soluble organic matrix subfractions, composed of low molecular weight molecules. Mollusk shell nacre contains molecules capable of reducing osteoclast bone resorption activity by inhibiting cathepsin K, giving a new facet of the bioactivity of nacre as bone biomaterial.
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