Collagen/annexin V interactions regulate chondrocyte mineralization.
Physiological mineralization in growth plate cartilage is highly regulated and restricted to terminally differentiated chondrocytes. Because mineralization occurs in the extracellular matrix, we asked whether major extracellular matrix components (collagens) of growth plate cartilage are directly involved in regulating the mineralization process. Our findings show that types II and X collagen interacted with cell surface-expressed annexin V. These interactions led to a stimulation of annexin V-mediated Ca(2+) influx resulting in an increased intracellular Ca(2+) concentration, [Ca(2+)](i), and ultimately increased alkaline phosphatase activity and mineralization of growth plate chondrocytes. Consequently, stimulation of these interactions (ascorbate to stimulate collagen synthesis, culturing cells on type II collagen-coated dishes, or overexpression of full-length annexin V) resulted in increase of [Ca(2+)](i), alkaline phosphatase activity, and mineralization of growth plate chondrocytes, whereas inhibition of these interactions (3,4-dehydro-l-proline to inhibit collagen secretion, K-201, a specific annexin channel blocker, overexpression of N terminus-deleted mutant annexin V that does not bind to type II collagen and shows reduced Ca(2+) channel activities) decreased [Ca(2+)](i), alkaline phosphatase activity, and mineralization. In conclusion, the interactions between collagen and annexin V regulate mineralization of growth plate cartilage. Because annexin V is up-regulated during pathological mineralization events of articular cartilage, it is possible that these interactions also regulate pathological mineralization.
Kim
Hyon Jong
HJ
Musculoskeletal Research Laboratories, Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Kirsch
Thorsten
T
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017304:Annexin A5 / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism; D002470:Cell Survival; D002642:Chick Embryo; D019902:Chondrocytes / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry*; D024043:Collagen Type II / Q000737:chemistry; D024121:Collagen Type X / Q000737:chemistry; D003600:Cytosol / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D017434:Protein Structure, Tertiary
D017304:Annexin A5; D024043:Collagen Type II; D024121:Collagen Type X; D008081:Liposomes; D003094:Collagen; D000469:Alkaline Phosphatase; D002118:Calcium