Enhanced load adaptation in long bone of cathepsin K-deficient mice

2014 ◽  
Author(s):  
Nicolas Bonnet ◽  
Lee Duong ◽  
Serge Ferrari
Keyword(s):  
Cathepsin K ◽  
Long Bone ◽  
Deficient Mice

Impaired bone resorption in cathepsin K-deficient mice is partially compensated for by enhanced osteoclastogenesis and increased expression of other proteases via an increased RANKL/OPG ratio

Bone ◽  
2005 ◽  
Vol 36 (1) ◽  
pp. 159-172 ◽  
Author(s):  
Riku Kiviranta ◽  
Jukka Morko ◽  
Sari L. Alatalo ◽  
Roisin NicAmhlaoibh ◽  
Juha Risteli ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Cathepsin K ◽  
Deficient Mice

scholarly journals Leptin Mediated Pathways Stabilize Posttraumatic Insulin and Osteocalcin Patterns after Long Bone Fracture and Concomitant Traumatic Brain Injury and Thus Influence Fracture Healing in a Combined Murine Trauma Model

2020 ◽  
Vol 21 (23) ◽  
pp. 9144
Author(s):  
Anja Garbe ◽  
Frank Graef ◽  
Jessika Appelt ◽  
Katharina Schmidt-Bleek ◽  
Denise Jahn ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Fracture Healing ◽  
Bone Fracture ◽  
Long Bone ◽  
Mouse Strains ◽  
Leptin Deficiency ◽  
Long Bone Fracture ◽  
Trauma Model ◽  
Deficient Mice

Recent studies on insulin, leptin, osteocalcin (OCN), and bone remodeling have evoked interest in the interdependence of bone formation and energy household. Accordingly, this study attempts to investigate trauma specific hormone changes in a murine trauma model and its influence on fracture healing. Thereunto 120 female wild type (WT) and leptin-deficient mice underwent either long bone fracture (Fx), traumatic brain injury (TBI), combined trauma (Combined), or neither of it and therefore served as controls (C). Blood samples were taken weekly after trauma and analyzed for insulin and OCN concentrations. Here, WT-mice with Fx and, moreover, with combined trauma showed a greater change in posttraumatic insulin and OCN levels than mice with TBI alone. In the case of leptin-deficiency, insulin changes were still increased after bony lesion, but the posttraumatic OCN was no longer trauma specific. Four weeks after trauma, hormone levels recovered to normal/basal line level in both mouse strains. Thus, WT- and leptin-deficient mice show a trauma specific hyperinsulinaemic stress reaction leading to a reduction in OCN synthesis and release. In WT-mice, this causes a disinhibition and acceleration of fracture healing after combined trauma. In leptin-deficiency, posttraumatic OCN changes are no longer specific and fracture healing is impaired regardless of the preceding trauma.

Characterisation and metabolism of astroglia-rich primary cultures from cathepsin K-deficient mice

2012 ◽  
Vol 393 (9) ◽  
pp. 959-970 ◽  
Author(s):  
Stephanie Dauth ◽  
Maike M. Schmidt ◽  
Maren Rehders ◽  
Frank Dietz ◽  
Sørge Kelm ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Primary Cultures ◽  
Cathepsin K ◽  
Wild Type ◽  
Glutathione S Transferase ◽  
Support Functions ◽  
Brain Functions ◽  
Myelin Associated Glycoprotein ◽  
Glutamyl Transpeptidase ◽  
Deficient Mice

Abstract Cathepsin K is important for the brain, because its deficiency in mice is associated with a marked decrease in differentiated astrocytes and changes in neuronal patterning in the hippocampus as well as with learning and memory deficits. As cathepsin K activity is most prominent in hippocampal regions of wild type animals, we hypothesised alterations in astrocyte-mediated support of neurons as a potential mechanism underlying the impaired brain functions in cathepsin K-deficient mice. To address this hypothesis, we have generated and characterised astroglia-rich primary cell cultures from cathepsin K-deficient and wild type mice and compared these cultures for possible changes in metabolic support functions and cell composition. Interestingly, cells expressing the oligodendrocytic markers myelin-associated glycoprotein and myelin basic protein were more frequent in astroglia-rich cultures from cathepsin K-deficient mice. However, cell cultures from both genotypes were morphologically comparable and similar with respect to glucose metabolism. In addition, specific glutathione content, glutathione export and γ-glutamyl-transpeptidase activity remained unchanged, whereas the specific activities of glutathione reductase and glutathione-S-transferase were increased by around 50% in cathepsin K-deficient cultures. Thus, lack of cathepsin K in astroglia-rich cultures appears not to affect metabolic supply functions of astrocytes but to facilitate the maturation of oligodendrocytes.

scholarly journals The Blimp1–Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis

2010 ◽  
Vol 207 (4) ◽  
pp. 751-762 ◽  
Author(s):  
Yoshiteru Miyauchi ◽  
Ken Ninomiya ◽  
Hiroya Miyamoto ◽  
Akemi Sakamoto ◽  
Ryotaro Iwasaki ◽  
...  
Keyword(s):  
B Lymphocyte ◽  
Transmembrane Protein ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
B Cell Lymphoma ◽  
Bone Homeostasis ◽  
Activated T Cells ◽  
Novel Therapeutic Strategies ◽  
Deficient Mice

Controlling osteoclastogenesis is critical to maintain physiological bone homeostasis and prevent skeletal disorders. Although signaling activating nuclear factor of activated T cells 1 (NFATc1), a transcription factor essential for osteoclastogenesis, has been intensively investigated, factors antagonistic to NFATc1 in osteoclasts have not been characterized. Here, we describe a novel pathway that maintains bone homeostasis via two transcriptional repressors, B cell lymphoma 6 (Bcl6) and B lymphocyte–induced maturation protein-1 (Blimp1). We show that Bcl6 directly targets ‘osteoclastic’ molecules such as NFATc1, cathepsin K, and dendritic cell-specific transmembrane protein (DC-STAMP), all of which are targets of NFATc1. Bcl6-overexpression inhibited osteoclastogenesis in vitro, whereas Bcl6-deficient mice showed accelerated osteoclast differentiation and severe osteoporosis. We report that Bcl6 is a direct target of Blimp1 and that mice lacking Blimp1 in osteoclasts exhibit osteopetrosis caused by impaired osteoclastogenesis resulting from Bcl6 up-regulation. Indeed, mice doubly mutant in Blimp1 and Bcl6 in osteoclasts exhibited decreased bone mass with increased osteoclastogenesis relative to osteoclast-specific Blimp1-deficient mice. These results reveal a Blimp1–Bcl6–osteoclastic molecule axis, which critically regulates bone homeostasis by controlling osteoclastogenesis and may provide a molecular basis for novel therapeutic strategies.

scholarly journals The Thyroid Hormone Transporter Mct8 Restricts Cathepsin-Mediated Thyroglobulin Processing in Male Mice through Thyroid Auto-Regulatory Mechanisms That Encompass Autophagy

2021 ◽  
Vol 22 (1) ◽  
pp. 462
Author(s):  
Vaishnavi Venugopalan ◽  
Alaa Al-Hashimi ◽  
Maren Rehders ◽  
Janine Golchert ◽  
Vivien Reinecke ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Cathepsin L ◽  
Cathepsin K ◽  
Regulatory Mechanisms ◽  
Classical Pathway ◽  
Phenotypic Differences ◽  
Pituitary Thyroid Axis ◽  
Data Points ◽  
Thyroid Axis ◽  
Deficient Mice

The thyroid gland is both a thyroid hormone (TH) generating as well as a TH responsive organ. It is hence crucial that cathepsin-mediated proteolytic cleavage of the precursor thyroglobulin is regulated and integrated with the subsequent export of TH into the blood circulation, which is enabled by TH transporters such as monocarboxylate transporters Mct8 and Mct10. Previously, we showed that cathepsin K-deficient mice exhibit the phenomenon of functional compensation through cathepsin L upregulation, which is independent of the canonical hypothalamus-pituitary-thyroid axis, thus, due to auto-regulation. Since these animals also feature enhanced Mct8 expression, we aimed to understand if TH transporters are part of the thyroid auto-regulatory mechanisms. Therefore, we analyzed phenotypic differences in thyroid function arising from combined cathepsin K and TH transporter deficiencies, i.e., in Ctsk-/-/Mct10-/-, Ctsk-/-/Mct8-/y, and Ctsk-/-/Mct8-/y/Mct10-/-. Despite the impaired TH export, thyroglobulin degradation was enhanced in the mice lacking Mct8, particularly in the triple-deficient genotype, due to increased cathepsin amounts and enhanced cysteine peptidase activities, leading to ongoing thyroglobulin proteolysis for TH liberation, eventually causing self-thyrotoxic thyroid states. The increased cathepsin amounts were a consequence of autophagy-mediated lysosomal biogenesis that is possibly triggered due to the stress accompanying intrathyroidal TH accumulation, in particular in the Ctsk-/-/Mct8-/y/Mct10-/- animals. Collectively, our data points to the notion that the absence of cathepsin K and Mct8 leads to excessive thyroglobulin degradation and TH liberation in a non-classical pathway of thyroid auto-regulation.

scholarly journals Ablation of Cathepsin K Activity in the Young Mouse Causes Hypermineralization of Long Bone and Growth Plates

2009 ◽  
Vol 84 (3) ◽  
pp. 229-239 ◽  
Author(s):  
Adele L. Boskey ◽  
Bruce D. Gelb ◽  
Eric Pourmand ◽  
Valery Kudrashov ◽  
Stephen B. Doty ◽  
...  
Keyword(s):  
Cathepsin K ◽  
Young Mouse ◽  
Long Bone ◽  
Growth Plates ◽  
K Activity
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