The effects of inhibitors of cysteine-proteinases and collagenase on the resorptive activity of isolated osteoclasts☆

Delaissé, Jean‐Marie; Boyde, A.; Maconnachie, E.; Ali, Nadire N.; Sear, Christopher H. J.; Eeckhout, Yves; Vaes, Gilbert; Jones, S. J.

doi:10.1016/8756-3282(87)90007-x

Cited by 175 publications

(88 citation statements)

References 36 publications

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“…MMP-13 has been suggested to contribute to bone resorption because the protease was detected in the resorption lacunae of the osteoclast and is able to catalyze the breakdown of collagen type I. 20 In tissues surrounding aseptically loosened endoprostheses, MMP-13 was localized in macrophages, fibroblasts, and endothelial cells. 21 Despite ample evidence for the presence of MMP-13 in interface tissues, it is not known which cell type expresses the protease.…”

Section: Discussionmentioning

confidence: 99%

Interface membrane fibroblasts around aseptically loosened endoprostheses express MMP‐13

Wagner

Gollwitzer

Wernicke

et al. 2007

Journal Orthopaedic Research

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The objective of this article was to assess whether matrix metalloproteinase-13 (MMP-13) is produced by cells of the peri-implant interface tissues and to further characterize these cells. Tissue specimens were collected from the bone-prosthesis interface at the time of revision surgery of clinically loosened hip and knee arthroplasties (n ¼ 27). Synovial tissues from osteoarthritic patients and young patients with mild joint deformity were used as controls (n ¼ 6). Tissue samples were fixed in 4% PFA, decalcified with EDTA, and embedded in paraffin. Sections (4 mm) were stained with hematoxylin/eosin and for the osteoclastic marker enzyme tartrate resistant acid phosphatase. Monocytes/macrophages were characterized with a monoclonal antibody against CD68 and mRNAs encoding MMP-13 and a 1 collagen I (COL1A1) were detected by in situ hybridization. Cells expressing transcripts encoding MMP-13 were found in 70% of the interface tissues. These cells colocalized with a cell population expressing COL1A1 mRNA, and were fibroblastic in appearance. MMP-13 expressing cells were found in the close vicinity of osteoclasts and multinuclear giant cells. No signals for transcripts encoding MMP-13 were detected in multinuclear giant cells or in osteoclasts. Control tissues were negative for transcripts encoding MMP-13 mRNA. Fibroblasts of the interface from aseptically loosened endoprostheses selectively express MMP-13. By the expression and the release of MMP-13, these fibroblastic cells may contribute to the local degradation of the extracellular matrix and to bone resorption. ß

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Section: Discussionmentioning

confidence: 99%

Interface membrane fibroblasts around aseptically loosened endoprostheses express MMP‐13

Wagner

Gollwitzer

Wernicke

et al. 2007

Journal Orthopaedic Research

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“…Cysteine protease inhibitors have been shown to be effective as anti-resorptive agents in cell-based bone resorption assays (Delaisse et al, 1987;Everts et al, 1988;Hill et al, 1994).…”

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confidence: 99%

Expression of human cathepsin K in Pichia pastoris and preliminary crystallographic studies of an inhibitor complex

et al. 1997

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Cathepsin K is a cysteine protease of the papain family, which is predominantly expressed in osteoclasts, and is regarded as a key protease in bone remodeling. To facilitate structural studies of the protein, the wild-type sequence of the protease has been mutated so as to replace a potential N-glycosylation site. We have expressed the mutant human cathepsin K to 190 mg/5 L using the Pichia pastoris expression system. Cathepsin K was inactivated with the mechanism-based inhibitor, APC3328, and crystallized from magnesium formate. A 2.2 8, X-ray data set has been collected on crystals belonging to space group P 2 1 2~2~. with a = 41.66 A, b = 5 1.41 A, and c = 107.72 A. There is most likely one molecule per asymmetric unit.

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“…These protons are thought to be involved in not only the degradation of bone mineral, chiefly solid calcium hydroxyapatite, but also in activation of cysteine proteinases by acidification of the lacunae. The lysosomal proteinases secreted into the lacunae, possibly cysteine proteinases, have been thought to play an important role in osseous collagenolysis [1,[3][4][5][6][7][8] We previously reported [9] that the bone pit formation stimulated by PTH was significantly suppressed by specific inhibitors of cathepsin L and L-type proteinases, but not by those of cathepsins B and D. Moreover, we also demonstrated [10] that the increase in pit formation stimulated by PTH paralleled the increase of a 39 kDa precursor form of cathepsin L secreted into media, and that both increases induced by PTH were markedly inhibited by addition of calcitonin. These findings indicate that the secretion of procathepsin L from osteoclasts is an important process in PTH-induced bone resorption.…”

Section: Introductionmentioning

confidence: 99%

Secretion and processing mechanisms of procathepsin L in bone resorption

Kakegawa¹,

Tagami²,

Ohba³

et al. 1995

FEBS Letters

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Secretion of procathepsin L into the culture medium from a bone cell mixture was markedly enhanced by addition of parathyroid hormone (PTH), 1 a,25-(OH)2D 3 or tumor necrosis factor a (TNFa). These stimulators of secretion of procathepsin L enhanced bone pit formation, which was inhibited by E-64, but not by CA-074, a specific inhibitor of cathepsin B. Procathepsin L may thus participate in the process of bone collagenolysis during bone resorption. Procathepsin L partially purified from rat long bones under cold conditions was rapidly converted to the mature form under acidic conditions at room temperature. This conversion was inhibited by E-64, suggesting that the procathepsin L secreted into lacunae is catalytically converted to the mature enzyme by cysteine proteinase(s).In the present study, designed to clarify the mechanism and regulation of both the secretion of procathepsin L and its processing in lacunae, we examined the secretion of procathepsin L induced by 10~,25-(OH)2D 3, TNFc~ or by PTH, and also the effects of the cysteine proteinase inhibitors, E-64 and CA-074, on the pit formation induced by these effectors. Furthermore, to clarify the participation of cysteine proteinase(s) in processing from the precursor to the active form, the inhibitory effect of E-64 on the processing of procathepsin L partially purified from rat long bones was also examined. Experimental

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The effects of inhibitors of cysteine-proteinases and collagenase on the resorptive activity of isolated osteoclasts☆

Cited by 175 publications

References 36 publications

Interface membrane fibroblasts around aseptically loosened endoprostheses express MMP‐13

Interface membrane fibroblasts around aseptically loosened endoprostheses express MMP‐13

Expression of human cathepsin K in Pichia pastoris and preliminary crystallographic studies of an inhibitor complex

Secretion and processing mechanisms of procathepsin L in bone resorption

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