Article

Human osteoblasts produce cathepsin K

Institute of Biomedicine/Anatomy, Biomedicum Helsinki, PO Box 63, FI-00014 University of Helsinki, Finland.
Bone (Impact Factor: 3.97). 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]. "

    Full-text · Dataset · Feb 2015
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    • "Cathepsin K is one of the main collagenolytic proteinase in osteoclasts. Recently, it has been shown that osteoblasts produce cathepsin K which may contribute to collagenous matrix maintenance and recycling of improperly processed collagen I [23]. One limitation of our study is that resource of the cathepsinK expression was not investigated, albeit it was recognized as an osteoclast marker previously. "
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    ABSTRACT: Arterial medial calcification (AMC) is frequent prevalence in patients with end stage renal disease. Evidence about hyperphosphatemia induced anabolic crosstalk between osteoblast and osteoclast in AMC of uremia is rare. Lanthanum carbonate as an orally administered phosphate-binding agent to reduce phosphate load and ameliorate AMC, but direct evidence is missing. Detailed time-course studies were conducted of Sprague-Dawley rats fed with adenine and high phosphate diet to imitate the onset and progression of AMC of uremia. Calcification in great arteries was evaluated by VonKossa's and Masson's trichrome staining. Osteoblast (Runx2, Osteocalcin) and osteoclast (RANKL, Cathepsin K, TRAP) related genes were analyzed by Immunohistochemistry and qRT-PCR. Serum PTH, RANKL and OPG levels were detected by ELISA kit. Serum phosphate was markedly increased in CRF group (6.94 +/- 0.97 mmol/L) and 2%La group (5.12 +/- 0.84 mmol/L) at week 4, while the latter group diminished significantly (2.92 +/- 0.73 mmol/L vs CRF Group 3.48 +/- 0.69, p < 0.01) at week 10. The rats that did not receive 2%La treatment had extensive von kossa staining for medial calcification in CRF group. In contrast, the rats in 2%La group just exhibit mild medial calcification. Inhibitory effect on progression of AMC was reflected by down regulated osteogenic genes and altered osteoclast-like genes. RANKL/OPG ratio in local calcification area was declined in 2%La group (vs CRF group, p <0.01), whereas marginal difference in serum among the three groups. In contrast to the robust expression of cathepsinK in calcified area, TRAP expression was not found. Abnormal phosphate homeostasis, induction of osteogenic conversion and osteoclast suppression were contributed to the current mechanisms of uremia associated arterial medial calcification based on our studies. Beneficial effects of Lanthanum carbonate could be mainly due to the decreased phosphate retention and cross-talk between osteoblast and osteoclast-like cell, both of which can be the therapeutic target for uremia associated with AMC.
    Full-text · Article · Dec 2013 · Journal of Translational Medicine
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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]. "

    Full-text · Dataset · Nov 2013
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