Staphylococcus aureus enhances osteoclast differentiation and bone resorption by stimulating the NLRP3 inflammasome pathway.
Humans
Osteoclasts
/ metabolism
Staphylococcus aureus
/ metabolism
NF-kappa B
/ metabolism
Inflammasomes
/ metabolism
NLR Family, Pyrin Domain-Containing 3 Protein
/ genetics
Matrix Metalloproteinase 9
/ genetics
Cathepsin K
Receptors, Calcitonin
/ metabolism
Cell Differentiation
Bone Resorption
/ metabolism
Osteogenesis
p38 Mitogen-Activated Protein Kinases
/ metabolism
NLRP3 inflammasome
Osteoclasts
Osteomyelitis
Staphylococcus aureus
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
28
07
2023
accepted:
05
10
2023
medline:
10
11
2023
pubmed:
11
10
2023
entrez:
10
10
2023
Statut:
ppublish
Résumé
Osteomyelitis is one of the most challenging infectious diseases and is mainly caused by Staphylococcus aureus (S. aureus). In this study, we analyzed the effect of S. aureus on osteoclast differentiation and its possible molecular mechanism. We cultured RAW 264.7 cells with live S. aureus for 5 days. We assessed cell viability and the formation of resorption pits. We tested the NLRP3 inflammasome signaling pathways and measured the mRNA expression levels of osteoclastspecific genes, including TRAP, MMP9, cathepsin K, calcitonin receptor and ATP6V0d2. Furthermore, we analyzed the protein expression levels of the protein in the NF-κB and p38 MAPK signaling pathways to clarify the signaling pathways by which S. aureus promotes osteoclast differentiation. Staphylococcus aureus induced NLRP3 inflammasome activation. S. aureus promoted bone resorption and enhanced the expression of osteoclastspecific genes, such as TRAP, MMP9, cathepsin K, calcitonin receptor and ATP6V0d2. MCC950 was used to inhibit NLRP3 inflammasome activity. Osteoclast differentiation and the expression of osteoclastspecific genes induced by S. aureus were inhibited by MCC950 pretreatment. The degradation of IκBα and phosphorylation of P65 were increased under the induction of S. aureus, but proteins in the p38 MAPK signaling pathway did not change significantly. Staphylococcus aureus induces osteoclast differentiation and promotes bone resorption in vitro, and the NLRP3 inflammasome signaling pathway plays a significant role in this process. S. aureus-induced NLRP3 inflammasome activation was mainly dependent on the NF-κB signaling pathway during osteoclastogenesis.
Sections du résumé
BACKGROUND
BACKGROUND
Osteomyelitis is one of the most challenging infectious diseases and is mainly caused by Staphylococcus aureus (S. aureus). In this study, we analyzed the effect of S. aureus on osteoclast differentiation and its possible molecular mechanism.
METHODS
METHODS
We cultured RAW 264.7 cells with live S. aureus for 5 days. We assessed cell viability and the formation of resorption pits. We tested the NLRP3 inflammasome signaling pathways and measured the mRNA expression levels of osteoclastspecific genes, including TRAP, MMP9, cathepsin K, calcitonin receptor and ATP6V0d2. Furthermore, we analyzed the protein expression levels of the protein in the NF-κB and p38 MAPK signaling pathways to clarify the signaling pathways by which S. aureus promotes osteoclast differentiation.
RESULTS
RESULTS
Staphylococcus aureus induced NLRP3 inflammasome activation. S. aureus promoted bone resorption and enhanced the expression of osteoclastspecific genes, such as TRAP, MMP9, cathepsin K, calcitonin receptor and ATP6V0d2. MCC950 was used to inhibit NLRP3 inflammasome activity. Osteoclast differentiation and the expression of osteoclastspecific genes induced by S. aureus were inhibited by MCC950 pretreatment. The degradation of IκBα and phosphorylation of P65 were increased under the induction of S. aureus, but proteins in the p38 MAPK signaling pathway did not change significantly.
CONCLUSION
CONCLUSIONS
Staphylococcus aureus induces osteoclast differentiation and promotes bone resorption in vitro, and the NLRP3 inflammasome signaling pathway plays a significant role in this process. S. aureus-induced NLRP3 inflammasome activation was mainly dependent on the NF-κB signaling pathway during osteoclastogenesis.
Identifiants
pubmed: 37817024
doi: 10.1007/s11033-023-08900-9
pii: 10.1007/s11033-023-08900-9
doi:
Substances chimiques
NF-kappa B
0
Inflammasomes
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Matrix Metalloproteinase 9
EC 3.4.24.35
Cathepsin K
EC 3.4.22.38
Receptors, Calcitonin
0
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9395-9403Subventions
Organisme : Natural Science Foundation of Fujian Province
ID : 2018J05149
Organisme : a grant from the Shanghai Municipal Health Commission
ID : 20204Y0430
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Almangour TA, Alhifany AA (2020) Dalbavancin for the management of osteomyelitis: a major step forward? J Antimicrob Chemother 75:2717–2722
doi: 10.1093/jac/dkaa188
pubmed: 32457989
Lew DP, Waldvogel FA (2004) Osteomyelitis. Lancet 364:369–379
doi: 10.1016/S0140-6736(04)16727-5
pubmed: 15276398
Speziale P, Pietrocola G (2020) The multivalent role of fibronectin-binding proteins a and B (FnBPA and FnBPB) of Staphylococcus aureus in host infections. Front Microbiol 11:2054
doi: 10.3389/fmicb.2020.02054
pubmed: 32983039
pmcid: 7480013
Gallarate M, Chirio D, Chindamo G et al (2020) Osteomyelitis: focus on conventional treatments and innovative drug delivery systems. Curr Drug Deliv 14:1.567201817666201e+24
Nasser A, Azimi T, Ostadmohammadi S (2020) A comprehensive review of bacterial osteomyelitis with emphasis on Staphylococcus aureus. Microb Pathog 148:104431
doi: 10.1016/j.micpath.2020.104431
pubmed: 32801004
Urish KL, Cassat JE (2020) Staphylococcus aureus osteomyelitis: bone, bugs, and surgery. Infect Immun 88:00919–00932
doi: 10.1128/IAI.00932-19
Ting JP, Lovering RC, Alnemri ES et al (2008) The NLR gene family: a standard nomenclature. Immunity 28:285–287
doi: 10.1016/j.immuni.2008.02.005
pubmed: 18341998
pmcid: 2630772
Zhang X, Dai J, Li L et al (2017) NLRP3 inflammasome expression and signaling in human diabetic wounds and in high glucose induced macrophages. J Diabetes Res 2017:5281358
doi: 10.1155/2017/5281358
pubmed: 28164132
pmcid: 5259616
Dai J, Chen H, Chai Y (2019) Advanced glycation end products (AGEs) induce apoptosis of fibroblasts by activation of NLRP3 inflammasome via reactive oxygen species (ROS) signaling pathway. Med Sci Monit 25:7499–7508
doi: 10.12659/MSM.915806
pubmed: 31587010
pmcid: 6792499
Putnam NE, Fulbright LE, Curry JM et al (2019) MyD88 and IL-1R signaling drive antibacterial immunity and osteoclast-driven bone loss during Staphylococcus aureus osteomyelitis. PLoS Pathog 15:e1007744
doi: 10.1371/journal.ppat.1007744
pubmed: 30978245
pmcid: 6481883
Craven RR, Gao X, Allen IC et al (2009) Staphylococcus aureus alpha-hemolysin activates the NLRP3-inflammasome in human and mouse monocytic cells. PLoS ONE 4:0007446
doi: 10.1371/journal.pone.0007446
Alippe Y, Wang C, Ricci B et al (2017) Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation. Sci Rep 7:07014–07017
doi: 10.1038/s41598-017-07014-0
Perera AP, Fernando R, Shinde T et al (2018) MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice. Sci Rep 8:8618
doi: 10.1038/s41598-018-26775-w
pubmed: 29872077
pmcid: 5988655
Xu Q, Chen G, Liu X et al (2019) Icariin inhibits RANKL-induced osteoclastogenesis via modulation of the NF-κB and MAPK signaling pathways. Biochem Biophys Res Commun 508:902–906
doi: 10.1016/j.bbrc.2018.11.201
pubmed: 30538045
Dore RK (2011) The RANKL pathway and denosumab. Rheum Dis Clin North Am 37:433–452, vi–vii
doi: 10.1016/j.rdc.2011.07.004
pubmed: 22023901
Xiao Y, Cao Y, Song C et al (2020) Cellular study of the LPS-induced osteoclastic multinucleated cell formation from RAW264.7 cells. J Cell Physiol 235:421–428
doi: 10.1002/jcp.28982
pubmed: 31222739
Feng X, McDonald JM (2011) Disorders of bone remodeling. Annu Rev Pathol 6:121–145
doi: 10.1146/annurev-pathol-011110-130203
pubmed: 20936937
pmcid: 3571087
Chen W, Tang P, Fan S et al (2022) A novel inhibitor INF 39 promotes osteogenesis via blocking the NLRP3/IL-1β axis. Biomed Res Int 2022:7250578
pubmed: 35872849
pmcid: 9300331
Josse J, Velard F, Gangloff SC (2015) Staphylococcus aureus vs. osteoblast: relationship and consequences in osteomyelitis. Front Cell Infect Microbiol 5:85
doi: 10.3389/fcimb.2015.00085
pubmed: 26636047
pmcid: 4660271
Mödinger Y, Löffler B, Huber-Lang M et al (2018) Complement involvement in bone homeostasis and bone disorders. Semin Immunol 37:53–65
doi: 10.1016/j.smim.2018.01.001
pubmed: 29395681
McCall SH, Sahraei M, Young AB et al (2008) Osteoblasts express NLRP3, a nucleotide-binding domain and leucine-rich repeat region containing receptor implicated in bacterially induced cell death. J Bone Miner Res 23:30–40
doi: 10.1359/jbmr.071002
pubmed: 17907925
Rasigade JP, Trouillet-Assant S, Ferry T et al (2013) PSMs of hypervirulent Staphylococcus aureus act as intracellular toxins that kill infected osteoblasts. PLoS ONE 8:e63176
doi: 10.1371/journal.pone.0063176
pubmed: 23690994
pmcid: 3653922
Ji Z, Su J, Hou Y et al (2020) EGFR/FAK and c-Src signalling pathways mediate the internalisation of Staphylococcus aureus by osteoblasts. Cell Microbiol 22:6
doi: 10.1111/cmi.13240
Wang J, Guan H, Liu H et al (2020) Inhibition of PFKFB3 suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss. J Cell Mol Med 24:2294–2307
doi: 10.1111/jcmm.14912
pubmed: 31880389
Kebaier C, Chamberland RR, Allen IC et al (2012) Staphylococcus aureus α-hemolysin mediates virulence in a murine model of severe pneumonia through activation of the NLRP3 inflammasome. J Infect Dis 205:807–817
doi: 10.1093/infdis/jir846
pubmed: 22279123
pmcid: 3274379
Wang C, Qu C, Alippe Y et al (2016) Poly-ADP-ribosylation-mediated degradation of ARTD1 by the NLRP3 inflammasome is a prerequisite for osteoclast maturation. Cell Death Dis 7:58
doi: 10.1038/s41420-021-00444-w
Li Y, Ling J, Jiang Q (2021) Inflammasomes in alveolar bone loss. Front Immunol 12:691013
doi: 10.3389/fimmu.2021.691013
pubmed: 34177950
pmcid: 8221428
Alippe Y, Kress D, Ricci B et al (2021) Actions of the NLRP3 and NLRC4 inflammasomes overlap in bone resorption. FASEB J 35:e21837
doi: 10.1096/fj.202100767RR
pubmed: 34383985
Chen Y, Yang Q, Lv C et al (2021) NLRP3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation. Cell Prolif 54:e12973
doi: 10.1111/cpr.12973
pubmed: 33382502
Liang S, Nian Z, Shi K (2020) Inhibition of RIPK1/RIPK3 ameliorates osteoclastogenesis through regulating NLRP3-dependent NF-κB and MAPKs signaling pathways. Biochem Biophys Res Commun 526:1028–1035
doi: 10.1016/j.bbrc.2020.03.177
pubmed: 32321638
Li C, Yang Z, Li Z et al (2011) Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating RANKL-mediated NF-κB and MAPK signaling pathways. J Bone Miner Res 26:644–656
doi: 10.1002/jbmr.242
pubmed: 20814972
Ren LR, Wang ZH, Wang H et al (2017) Staphylococcus aureus induces osteoclastogenesis via the NF-κB signaling pathway. Med Sci Monit 23:4579–4590
doi: 10.12659/MSM.903371
pubmed: 28942456
pmcid: 5629995