Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase A2
Increasing evidence points to the involvement of group IIA secreted phospholipase A2 (sPLA2-IIA) in pathologies characterized by abnormal osteoclast bone-resorption activity. Here, the role of this moonlighting protein has been deepened in the osteoclastogenesis process driven by the RANKL cytokine...
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| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.966950/full |
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| author | Maria Mangini Rosa D’Angelo Caterina Vinciguerra Christine Payré Gérard Lambeau Barbara Balestrieri Julia F. Charles Stefania Mariggiò |
| author_facet | Maria Mangini Rosa D’Angelo Caterina Vinciguerra Christine Payré Gérard Lambeau Barbara Balestrieri Julia F. Charles Stefania Mariggiò |
| author_sort | Maria Mangini |
| collection | DOAJ |
| description | Increasing evidence points to the involvement of group IIA secreted phospholipase A2 (sPLA2-IIA) in pathologies characterized by abnormal osteoclast bone-resorption activity. Here, the role of this moonlighting protein has been deepened in the osteoclastogenesis process driven by the RANKL cytokine in RAW264.7 macrophages and bone-marrow derived precursor cells from BALB/cJ mice. Inhibitors with distinct selectivity toward sPLA2-IIA activities and recombinant sPLA2-IIA (wild-type or catalytically inactive forms, full-length or partial protein sequences) were instrumental to dissect out sPLA2-IIA function, in conjunction with reduction of sPLA2-IIA expression using small-interfering-RNAs and precursor cells from Pla2g2a knock-out mice. The reported data indicate sPLA2-IIA participation in murine osteoclast maturation, control of syncytium formation and resorbing activity, by mechanisms that may be both catalytically dependent and independent. Of note, these studies provide a more complete understanding of the still enigmatic osteoclast multinucleation process, a crucial step for bone-resorbing activity, uncovering the role of sPLA2-IIA interaction with a still unidentified receptor to regulate osteoclast fusion through p38 SAPK activation. This could pave the way for the design of specific inhibitors of sPLA2-IIA binding to interacting partners implicated in osteoclast syncytium formation. |
| first_indexed | 2024-12-10T19:35:45Z |
| format | Article |
| id | doaj.art-ec8e3023da9d4fa7b079b400af6c044f |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-10T19:35:45Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ec8e3023da9d4fa7b079b400af6c044f2022-12-22T01:36:09ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-08-011010.3389/fcell.2022.966950966950Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase A2Maria Mangini0Rosa D’Angelo1Caterina Vinciguerra2Christine Payré3Gérard Lambeau4Barbara Balestrieri5Julia F. Charles6Stefania Mariggiò7Institute of Protein Biochemistry, National Research Council, Naples, ItalyInstitute of Protein Biochemistry, National Research Council, Naples, ItalyInstitute of Biochemistry and Cell Biology, National Research Council, Naples, ItalyCentre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d’Azur, Valbonne Sophia Antipolis, FranceCentre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d’Azur, Valbonne Sophia Antipolis, FranceJeff and Penny Vinik Center for Translational Immunology Research, Department of Medicine, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDepartments of Orthopaedic Surgery and Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesInstitute of Protein Biochemistry, National Research Council, Naples, ItalyIncreasing evidence points to the involvement of group IIA secreted phospholipase A2 (sPLA2-IIA) in pathologies characterized by abnormal osteoclast bone-resorption activity. Here, the role of this moonlighting protein has been deepened in the osteoclastogenesis process driven by the RANKL cytokine in RAW264.7 macrophages and bone-marrow derived precursor cells from BALB/cJ mice. Inhibitors with distinct selectivity toward sPLA2-IIA activities and recombinant sPLA2-IIA (wild-type or catalytically inactive forms, full-length or partial protein sequences) were instrumental to dissect out sPLA2-IIA function, in conjunction with reduction of sPLA2-IIA expression using small-interfering-RNAs and precursor cells from Pla2g2a knock-out mice. The reported data indicate sPLA2-IIA participation in murine osteoclast maturation, control of syncytium formation and resorbing activity, by mechanisms that may be both catalytically dependent and independent. Of note, these studies provide a more complete understanding of the still enigmatic osteoclast multinucleation process, a crucial step for bone-resorbing activity, uncovering the role of sPLA2-IIA interaction with a still unidentified receptor to regulate osteoclast fusion through p38 SAPK activation. This could pave the way for the design of specific inhibitors of sPLA2-IIA binding to interacting partners implicated in osteoclast syncytium formation.https://www.frontiersin.org/articles/10.3389/fcell.2022.966950/fullgroup IIA secreted phospholipase A2 (sPLA2-IIA)p38 SAPKosteoclastogenesisosteoclast syncytiaLLKYK cyclic peptide |
| spellingShingle | Maria Mangini Rosa D’Angelo Caterina Vinciguerra Christine Payré Gérard Lambeau Barbara Balestrieri Julia F. Charles Stefania Mariggiò Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase A2 Frontiers in Cell and Developmental Biology group IIA secreted phospholipase A2 (sPLA2-IIA) p38 SAPK osteoclastogenesis osteoclast syncytia LLKYK cyclic peptide |
| title | Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase A2 |
| title_full | Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase A2 |
| title_fullStr | Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase A2 |
| title_full_unstemmed | Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase A2 |
| title_short | Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase A2 |
| title_sort | multimodal regulation of the osteoclastogenesis process by secreted group iia phospholipase a2 |
| topic | group IIA secreted phospholipase A2 (sPLA2-IIA) p38 SAPK osteoclastogenesis osteoclast syncytia LLKYK cyclic peptide |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.966950/full |
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