Effect of the selective cathepsin K inhibitor MIV-711 on bone resorption and cartilage degradation biomarkers and on knee joint pathology in dogs subjected to partial medial meniscectomy, an experimental model of osteoarthritis

Bone ◽  
2012 ◽  
Vol 50 ◽  
pp. S188-S189 ◽  
Author(s):  
E. Lindstrom⁎ ◽  
L. Vrang ◽  
S. Sedig ◽  
Y. Terelius ◽  
K. Wikström ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Knee Joint ◽  
Experimental Model ◽  
Cathepsin K ◽  
Cartilage Degradation ◽  
Cathepsin K Inhibitor ◽  
Joint Pathology ◽  
Medial Meniscectomy ◽  
And Cartilage

scholarly journals Protective effects of a cathepsin K inhibitor, SB-553484, in the canine partial medial meniscectomy model of osteoarthritis

2009 ◽  
Vol 17 (9) ◽  
pp. 1236-1243 ◽  
Author(s):  
J.R. Connor ◽  
C. LePage ◽  
B.A. Swift ◽  
D. Yamashita ◽  
A.M. Bendele ◽  
...  
Keyword(s):  
Cathepsin K ◽  
Protective Effects ◽  
Cathepsin K Inhibitor ◽  
Medial Meniscectomy

scholarly journals The selective cathepsin K inhibitor MIV-711 attenuates joint pathology in experimental animal models of osteoarthritis

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Erik Lindström ◽  
Biljana Rizoska ◽  
Karin Tunblad ◽  
Charlotte Edenius ◽  
Alison M. Bendele ◽  
...  
Keyword(s):  
Animal Models ◽  
Experimental Animal ◽  
Cathepsin K ◽  
Experimental Animal Models ◽  
Cathepsin K Inhibitor ◽  
Joint Pathology

scholarly journals NOD2 Contributes to Porphyromonas gingivalis–induced Bone Resorption

2014 ◽  
Vol 93 (11) ◽  
pp. 1155-1162 ◽  
Author(s):  
T.P. Prates ◽  
T.M. Taira ◽  
M.C. Holanda ◽  
L.A. Bignardi ◽  
S.L. Salvador ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Experimental Model ◽  
Porphyromonas Gingivalis ◽  
Quantitative Polymerase Chain Reaction ◽  
Muramyl Dipeptide ◽  
Cathepsin K ◽  
Gingival Tissue ◽  
Wild Type ◽  
Osteoclast Activity ◽  
Stimulation Of

The NOD-like receptors are cytoplasmic proteins that sense microbial by-products released by invasive bacteria. Although NOD1 and NOD2 are functionally expressed in cells from oral tissues and play a role triggering immune responses, the role of NOD2 receptor in the bone resorption and in the modulation of osteoclastogenesis is still unclear. We show that in an experimental model of periodontitis with Porphyromonas gingivalis W83, NOD2-/- mice showed lower bone resorption when compared to wild type. Quantitative polymerase chain reaction analysis revealed that wild-type infected mice showed an elevated RANKL/OPG ratio when compared to NOD2-/- infected mice. Moreover, the expression of 2 osteoclast activity markers—cathepsin K and matrix metalloproteinase 9—was significantly lower in gingival tissue from NOD2-/- infected mice compared to WT infected ones. The in vitro study reported an increase in the expression of the NOD2 receptor 24 hr after stimulation of hematopoietic bone marrow cells with M-CSF and RANKL. We also evaluated the effect of direct activation of NOD2 receptor on osteoclastogenesis, by the activation of this receptor in preosteoclasts culture, with different concentrations of muramyl dipeptide. The results show no difference in the number of TRAP-positive cells. Although it did not alter the osteoclasts differentiation, the activation of NOD2 receptor led to a significant increase of cathepsin K expression. We confirm that this enzyme was active, since the osteoclasts resorption capacity was enhanced by muramyl dipeptide stimulation, evaluated in osteoassay plate. These results show that the lack of NOD2 receptor impairs the bone resorption, suggesting that NOD2 receptor could contribute to the progression of bone resorption in experimental model of periodontitis. The stimulation of NOD2 by its agonist, muramyl dipeptide, did not affect osteoclastogenesis, but it does favor the bone resorption capacity identified by increased osteoclast activity.

Inhibition of bone resorption by the cathepsin K inhibitor odanacatib is fully reversible

Bone ◽  
2014 ◽  
Vol 67 ◽  
pp. 269-280 ◽  
Author(s):  
Y. Zhuo ◽  
J.-Y. Gauthier ◽  
W.C. Black ◽  
M.D. Percival ◽  
L.T. Duong
Keyword(s):  
Bone Resorption ◽  
Cathepsin K ◽  
Cathepsin K Inhibitor

scholarly journals Effect of TNF inhibitors with bisphosphonates vs bisphosphonates alone on bone mineral density and bone and cartilage biomarkers at 1 year in patients with rheumatoid arthritis: A prospective study

2021 ◽  
Author(s):  
Yuichi Nagase ◽  
Masakazu Nagashima ◽  
Kenichi Shimane ◽  
Takuji Nishikawa ◽  
Masashi Naito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Mineral Density ◽  
Bone Resorption ◽  
Bone Mineral ◽  
Matrix Protein ◽  
Cartilage Degradation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
And Cartilage ◽  
Cartilage Biomarkers

ABSTRACT Background The present study aimed prospectively to investigate the effect of a combination of tumour necrosis factor inhibitors and bisphosphonates (TNFi with BP) on bone mineral density (BMD) and bone and cartilage biomarkers compared to that of BP alone at 1 year in patients with rheumatoid arthritis (RA). Methods Two groups of patients with RA and osteoporosis were enrolled. One group (37 patients) had already received BP, while the other group (37 patients) had already received TNFi with BP. The serum bone resorption and formation markers, cartilage markers, BMD in the lumbar spine, femoral neck, and distal radius were prospectively investigated at the beginning of the study and at 6 and 12 months. Results The percentages of change recorded for the various assessment categories were as follows in the TNFi with BP group: (1) tartrate-resistant acid phosphatase-5b had significantly decreased and osteocalcin had increased; (2) matrix metalloproteinase-3 and cartilage oligomeric matrix protein had significantly decreased; and (3) each BMD did not differ significantly between the groups. Conclusion Our data suggested that TNFi with BP therapy not only suppressed cartilage degradation and bone resorption but also increased bone formation; however, this treatment did not affect the BMD at 1 year.

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