Annexin V/beta5 integrin interactions regulate apoptosis of growth plate chondrocytes.
Apoptosis of terminally differentiated chondrocytes allows the replacement of growth plate cartilage by bone. Despite its importance, little is known about the regulation of chondrocyte apoptosis. We show that overexpression of annexin V, which binds to the cytoplasmic domain of beta5 integrin and protein kinase C alpha (PKCalpha), stimulates apoptotic events in hypertrophic growth plate chondrocytes. To determine whether the balance between the interactions of annexin V/beta5 integrin and annexin V/active PKCalpha play a role in the regulation of terminally differentiated growth plate chondrocyte apoptosis, a peptide mimic of annexin V (Penetratin (Pen)-VVISYSMPD) that binds to beta5 integrin but not to PKCalpha was used. This peptide stimulated apoptotic events in growth plate chondrocytes. Suppression of annexin V expression using small interfering ribonucleic acid decreased caspase-3 activity and increased cell viability in Pen-VVISYSMPD-treated growth plate chondrocytes. An activator of PKC resulted in a further decrease of cell viability and further increase of caspase-3 activity in Pen-VVISYSMPD-treated growth plate chondrocytes, whereas inhibitors of PKCalpha led to an increase of cell viability and decrease of caspase-3 activity of Pen-VVISYSMPD-treated cells. These findings suggest that binding of annexin V to active PKCalpha stimulates apoptotic events in growth plate chondrocytes and that binding of annexin Vto beta5 integrin controls these interactions and ultimately apoptosis.
Wang
Wei
W
Musculoskeletal Research Laboratories, Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Kirsch
Thorsten
T
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002645:Chickens; D019902:Chondrocytes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006132:Growth Plate / Q000378:metabolism*; D039641:Integrin beta Chains / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D051571:Protein Kinase C-alpha / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D017304:Annexin A5; D039641:Integrin beta Chains; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C084344:integrin beta5; D051571:Protein Kinase C-alpha; D053148:Caspase 3