Secretory phospholipase A sub(2) promotes MMP-9-mediated cell death by degrading type I collagen via the ERK pathway at an early stage of chondrogenesis

Background information. sPLA sub(2) (secretory phospholipase A sub(2)) 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 sPLA sub(2) during chondrogenesis have not been studied. Results. In the present study, for the first time, we detect the secretion of sPLA sub(2) during limb development and suggest that sPLA sub(2) influences the proliferation and/or survival of limb mesenchymal cells. Treatment of wing bud mesenchymal cells with exogenous sPLA sub(2) 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 sPLA sub(2) were prevented by functional blocking of FcRY (chicken yolk sac IgY receptor), a mannose receptor family member that is the orthologue of the mammalian PLA sub(2) (phospholipase A sub(2)) receptor and by inhibition of ERK (extracellular-signal-regulated kinase) activity. Conclusions. Taken together, our results suggest that elevated levels of sPLA sub(2) 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.