1 Participation of Lysosomal Cathepsins in Antigen Processing and Bone Resorption

2015 ◽  
pp. 3-21
Author(s):  
Nobuhiko Katunuma
Keyword(s):  
Bone Resorption ◽  
Antigen Processing

scholarly journals A non-immunological role for γ-interferon–inducible lysosomal thiol reductase (GILT) in osteoclastic bone resorption

2021 ◽  
Vol 7 (17) ◽  
pp. eabd3684
Author(s):  
Benjamin W. Ewanchuk ◽  
Corey R. Arnold ◽  
Dale R. Balce ◽  
Priyatha Premnath ◽  
Tanis L. Orsetti ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Cysteine Protease ◽  
Antigen Processing ◽  
Matrix Protein ◽  
Direct Reduction ◽  
Bone Matrix ◽  
Cathepsin K ◽  
Dependent Manner ◽  
Thiol Reductase ◽  
Γ Interferon

The extracellular bone resorbing lacuna of the osteoclast shares many characteristics with the degradative lysosome of antigen-presenting cells. γ-Interferon–inducible lysosomal thiol reductase (GILT) enhances antigen processing within lysosomes through direct reduction of antigen disulfides and maintenance of cysteine protease activity. In this study, we found the osteoclastogenic cytokine RANKL drove expression of GILT in osteoclast precursors in a STAT1-dependent manner, resulting in high levels of GILT in mature osteoclasts, which could be further augmented by γ-interferon. GILT colocalized with the collagen-degrading cysteine protease, cathepsin K, suggesting a role for GILT inside the osteoclastic resorption lacuna. GILT-deficient osteoclasts had reduced bone-resorbing capacity, resulting in impaired bone turnover and an osteopetrotic phenotype in GILT-deficient mice. We demonstrated that GILT could directly reduce the noncollagenous bone matrix protein SPARC, and additionally, enhance collagen degradation by cathepsin K. Together, this work describes a previously unidentified, non-immunological role for GILT in osteoclast-mediated bone resorption.

Novel physiological functions of cathepsins B and L on antigen processing and osteoclastic bone resorption

1998 ◽  
Vol 38 (1) ◽  
pp. 235-251 ◽  
Author(s):  
N. Katunuma ◽  
Y. Matsunaga ◽  
A. Matsui ◽  
H. Kakegawa ◽  
K. Endo ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Antigen Processing ◽  
Osteoclastic Bone Resorption ◽  
Physiological Functions

Co-purification of bone resorbing activity and adenylate cyclase stimulating activity from human tumours associated with the humoral hypercalcaemia of malignancy

1987 ◽  
Vol 114 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Chohei Shigeno ◽  
Itsuo Yamamoto ◽  
Shegiharu Dokoh ◽  
Megumu Hino ◽  
Jun Aoki ◽  
...  
Keyword(s):  
Bone Resorption ◽  
High Performance ◽  
Basic Protein ◽  
Gel Filtration ◽  
Exchange Chromatography ◽  
Protein Factor ◽  
Human Tumours ◽  
Acid Stable ◽  
Bone Resorbing Activity

Abstract. We have partially purified a tumour factor capable of stimulating both bone resorption in vitro and cAMP accumulation in osteoblastic ROS 17/2 cells from three human tumours associated with humoral hypercalcaemia of malignancy. Purification of tumour factor by sequential acid urea extraction, gel filtration and cation-exchange chromatography, reverse-phase high performance liquid chromatography followed by analytical isoelectric focussing provided a basic protein (pI > 9.3) with a molecular weight of approximately 13 000 as a major component of the final preparation which retained both the two bioactivities. Bone resorbing activity and cAMP-increasing activity in purified factor correlated with each other. cAMP-increasing activity of the factor was heat- and acid-stable, but sensitive to alkaline ambient pH. Treatment with trypsin destroyed cAMP-increasing activity of the factor. Synthetic parathyroid hormone (PTH) antagonist, human PTH-(3– 34) completely inhibited the cAMP-increasing activity of the factor. The results suggest that this protein factor, having its effects on both osteoclastic and osteoblastic functions, may be involved in development of enhanced bone resorption in some patients with humoral hypercalcaemia of malignancy.

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