Secretory phospholipase A2 promotes MMP-9-mediated cell death by degrading type I collagen via the ERK pathway at an early stage of chondrogenesis.
BACKGROUND
sPLA2 (secretory phospholipase A2) has been implicated in a wide range of cellular responses, including cell proliferation and ECM (extracellular matrix) remodelling. Even though ECM remodelling is an essential step for chondrogenesis, the expression and functions of sPLA2 during chondrogenesis have not been studied.


RESULTS
In the present study, for the first time, we detect the secretion of sPLA2 during limb development and suggest that sPLA2 influences the proliferation and/or survival of limb mesenchymal cells. Treatment of wing bud mesenchymal cells with exogenous sPLA2 promoted cell death by activating MMP-9 (matrix metalloproteinase-9) and increasing type I collagen degradation. The additive chondro-inhibitory actions were induced by co-treatment of mp-BSA (p-aminophenyl-mannopyranoside-BSA), a known ligand of the mannose receptor. Chondro-inhibitory actions by sPLA2 were prevented by functional blocking of FcRY (chicken yolk sac IgY receptor), a mannose receptor family member that is the orthologue of the mammalian PLA2 (phospholipase A2) receptor and by inhibition of ERK (extracellular-signal-regulated kinase) activity.


CONCLUSIONS
Taken together, our results suggest that elevated levels of sPLA2 secreted by wing bud mesenchymal cells promote type I collagen degradation by MMP-9 in a manner typical of receptor-mediated signalling and that these events lead to cell death.
Choi
Young-Ae
YA
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.
Kim
Dong-Kyun
DK
Bang
Ok-Sun
OS
Kang
Shin-Sung
SS
Jin
Eun-Jung
EJ
D000818:Animals; D017209:Apoptosis; D030161:Avian Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis; D024042:Collagen Type I / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D054497:Phospholipases A2, Secretory / Q000378:metabolism*; D013997:Time Factors
D030161:Avian Proteins; D024042:Collagen Type I; D048049:Extracellular Signal-Regulated MAP Kinases; D054497:Phospholipases A2, Secretory; D020780:Matrix Metalloproteinase 9