Caspase-2 modulates osteoclastogenesis through down-regulating oxidative stress

Bone
Danielle A CallawayJean X Jiang

Abstract

The loss of caspase-2 (Casp-2) in mice results in an osteopenic phenotype associated with increased numbers of osteoclasts in vivo. In this study, we show that Casp-2 is involved in osteoclastogenesis. Protein levels of Casp-2 decrease during the differentiation of macrophages to osteoclasts. Furthermore, siRNA-mediated Casp-2 knockdown in osteoclast precursors or differentiation of bone marrow macrophage (BMM) precursors from Casp2(-/-) mice results in increased osteoclast numbers and tartrate-resistant acid phosphatase (TRAP) activity. Casp2(-/-) osteoclasts are larger in size compared to wild-type osteoclasts and exhibited increased numbers of nuclei, perhaps due to increased precursor fusion. The loss of Casp-2 did not alter earlier stages of differentiation, but had a greater consequence on later stages involving NFATc1 auto-amplification and pre-osteoclast fusion. We have previously shown that the loss of Casp-2 results in increased oxidative stress in the bone. Reactive oxygen species (ROS) is known to play a critical role in late osteoclast differentiation and we show that total ROS and specifically, mitochondrial ROS, significantly increased in Casp2(-/-) BMM precursors after RANKL administration, with a concomitant re...Continue Reading

References

Jun 30, 1992·Biochemical and Biophysical Research Communications·S KumarM Noda
Mar 1, 1990·The Journal of Clinical Investigation·I R GarrettG R Mundy
Jun 6, 1998·Genes & Development·L BergeronJ Yuan
Feb 8, 2002·The Journal of Biological Chemistry·Yin GuoEmad S Alnemri
Dec 17, 2002·The Journal of Biological Chemistry·Derick HanEnrique Cadenas
Nov 9, 2004·Experimental Cell Research·Hyunil HaZang Hee Lee
Jun 23, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Sridhar MuthusamiSrinivasan Narasimhan
Oct 11, 2005·Journal of Cellular Biochemistry·Eric C SealesJay M McDonald
Nov 9, 2005·The Journal of Experimental Medicine·Masataka AsagiriHiroshi Takayanagi
Nov 10, 2005·Menopause : the Journal of the North American Menopause Society·Farzad DeyhimBahram H Arjmandi
Sep 15, 2006·Journal of Cellular Physiology·K H SzymczykM J Steinbeck
Dec 26, 2006·Mechanisms of Ageing and Development·Yingpei ZhangBrian Herman
Jul 12, 2007·The Journal of Biological Chemistry·Maria AlmeidaStavros C Manolagas
Sep 8, 2007·Rheumatology International·Ozlem AltindagSahabettin Selek
May 30, 2008·Calcified Tissue International·So Young BuBrenda J Smith
Feb 18, 2010·Journal of Cellular and Molecular Medicine·Lisa Bouchier-Hayes
Apr 16, 2010·Annals of the New York Academy of Sciences·Satish SrinivasanNarayan G Avadhani
May 26, 2012·PloS One·Giuseppa PistrittoMaria Luisa Barbaccia
May 2, 2014·Nature Communications·Shoshana M BartellMaria Almeida

❮ Previous
Next ❯

Citations

May 18, 2020·Cell Death and Differentiation·Valentina C Sladky, Andreas Villunger
Jan 25, 2020·Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry·Mehmet Murat Taskan, Fikret Gevrek

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis