Skip to main content

Advertisement

SpringerLink
Log in

Substance P Exacerbates the Inflammatory and Pro-osteoclastogenic Responses of Murine Osteoclasts and Osteoblasts to Staphylococcus aureus

  • Original Article
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Staphylococcus aureus infections of bone tissue are associated with inflammatory bone loss. Resident bone cells, including osteoblasts and osteoclasts, can perceive S. aureus and produce an array of inflammatory and pro-osteoclastogenic mediators, thereby contributing to such damage. The neuropeptide substance P (SP) has been shown to exacerbate microbially induced inflammation at sites such as the gut and the brain and has previously been shown to affect bone cell differentiation and activity. Here we demonstrate that the interaction of SP with its high affinity receptor, neurokinin-1 receptor (NK-1R), expressed on murine osteoblasts and osteoclasts, augments the inflammatory responses of these cells to S. aureus challenge. Additionally, SP alters the production of pro- and anti-osteoclastogenic factors by bacterially challenged bone cells and their proteolytic functions in a manner that would be anticipated to exacerbate inflammatory bone loss at sites of infection. Furthermore, we have demonstrated that the clinically approved NK-1R antagonist, aprepitant, attenuates local inflammatory and pro-osteoclastogenic mediator expression in an in vivo mouse model of post-traumatic staphylococcal osteomyelitis. Taken together, these results indicate that SP/NK-1R interactions could play a significant role in the initiation and/or progression of damaging inflammation in S. aureus bone infections and suggest that the repurposing of currently approved NK-1R antagonists might represent a promising new adjunct therapy for such conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

DATA AVAILABILITY

Access to raw data will be available upon reasonable request after publication.

References

  1. Lew, Daniel P., and Francis A. Waldvogel. 2004. Osteomyelitis. Lancet 364. Elsevier B.V. 369–379. https://doi.org/10.1016/S0140-6736(04)16727-5.

  2. Urish, Kenneth L., and James E. Cassat. 2020. Staphylococcus aureus osteomyelitis: bone, bugs, and surgery. Infection and Immunity 88. https://doi.org/10.1128/IAI.00932-19

  3. Ben-Zvi, Lior, Jeremy Hassan, Marah andraous, Daniel Weltsch, Diklah Sebag, Michael Margulis, and Benjamin Bernfeld. 2021. Diagnosis and management of osteomyelitis in children. Current Infectious Disease Reports 23. Springer. https://doi.org/10.1007/S11908-021-00763-0.

  4. Gimza, Brittney D., and James E. Cassat. 2021. Mechanisms of antibiotic failure during Staphylococcus aureus osteomyelitis. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2021.638085.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Funk, Shawn S., and Lawson A.B. Copley. 2017. Acute hematogenous osteomyelitis in children: pathogenesis, diagnosis, and treatment. Orthopedic Clinics of North America 48. Elsevier: 199–208. https://doi.org/10.1016/J.OCL.2016.12.007.

  6. Gornitzky, Alex L., Arin E. Kim, Jennifer M. O’Donnell, and Ishaan Swarup. 2020. Diagnosis and management of osteomyelitis in children: a critical analysis review. JBJS Reviews 8. Journal of Bone and Joint Surgery Inc. https://doi.org/10.2106/JBJS.RVW.19.00202.

  7. Peyrani, P., M. Allen, D. Seligson, C. Roberts, A. Chen, N. Haque, M. Zervos, et al. 2012. Clinical outcomes of osteomyelitis patients infected with methicillin-resistant Staphylococcus aureus USA-300 strains. American journal of orthopedics (Belle Mead, N.J.) 41: 117–122.

  8. Arnold, Sandra R., David Elias, Steven C. Buckingham, Eddie D. Thomas, Eduardo Novais, Alexandre Arkader, and Cassandra Howard. 2006. Changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant Staphylococcus aureus. Journal of pediatric orthopedics 26. J Pediatr Orthop: 703–708. https://doi.org/10.1097/01.BPO.0000242431.91489.B4.

  9. Hatzenbuehler, John, and Thomas J. Pulling. 2011. Diagnosis and management of osteomyelitis. American Family Physician 84. American Academy of Family Physicians: 1027–1033. https://doi.org/10.2165/00019053-199916060-00003.

  10. Nair, Sean, Yu Song, Sajeda Meghji, Kris Reddi, Malcolm Harris, Alistair Ross, Stephen Poole, Michael Wilson, and Brian Henderson. 1995. Surface-associated proteins from Staphylococcus aureus demonstrate potent bone resorbing activity. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 10. J Bone Miner Res: 726–734. https://doi.org/10.1002/JBMR.5650100509.

  11. Meghji, S, S J Crean, P A Hill, M Sheikh, S P Nair, K Heron, B Henderson, E B Mawer, and M Harris. 1998. Surface-associated protein from Staphylococcus aureus stimulates osteoclastogenesis: possible role in S. aureus-induced bone pathology. British Journal of Rheumatology. Vol. 37.

  12. Sin, Lau, Yu., Wilson Wang, Afsaneh Sabokbar, Hamish Simpson, Sean Nair, Brian Henderson, Anthony Berendt, and Nicholas A. Athanasou. 2006. Staphylococcus aureus capsular material promotes osteoclast formation. Injury 37: 41–48. https://doi.org/10.1016/J.INJURY.2006.04.008.

    Article  Google Scholar 

  13. Madrazo, Denise R., Susanne L. Tranguch, and Ian Marriott. 2003. Signaling via toll-like receptor 5 can initiate inflammatory mediator production by murine osteoblasts. Infection and immunity 71: 5418–5421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chauhan, V.S., and I. Marriott. 2010. Differential roles for NOD2 in osteoblast inflammatory immune responses to bacterial pathogens of bone tissue. Journal of Medical Microbiology 59: 755–762. https://doi.org/10.1099/jmm.0.015859-0.

    Article  CAS  PubMed  Google Scholar 

  15. Marriott, I., D.M. Rati, S.H. McCall, and S.L. Tranguch. 2005. Induction of Nod1 and Nod2 intracellular pattern recognition receptors in murine osteoblasts following bacterial challenge. Infection and Immunity 73: 2967–2973. https://doi.org/10.1128/IAI.73.5.2967-2973.2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gasper, Nancy A., Cynthia C. Petty, Laura W. Schrum, Ian Marriott, and Kenneth L. Bost. 2002. Bacterium-induced CXCL10 secretion by osteoblasts can be mediated in part through toll-like receptor 4. Infection and immunity 70: 4075–4082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barton, Gregory M., and Ruslan Medzhitov. 2003. Toll-like receptor signaling pathways. Science 300: 1524–1525. https://doi.org/10.1126/SCIENCE.1085536.

    Article  CAS  PubMed  Google Scholar 

  18. Zou, Wei, Alla Amcheslavsky, and Zvi Bar-Shavit. 2003. CpG oligodeoxynucleotides modulate the osteoclastogenic activity of osteoblasts via toll-like receptor 9. Journal of Biological Chemistry 278: 16732–16740. https://doi.org/10.1074/JBC.M212473200.

    Article  CAS  PubMed  Google Scholar 

  19. Marriott, Ian, David L. Gray, Dana M. Rati, Vance G. Fowler, Martin E. Stryjewski, L. Scott Levin, Michael C. Hudson, and Kenneth L. Bost. 2005. Osteoblasts produce monocyte chemoattractant protein-1 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue. Bone 37: 504–512. https://doi.org/10.1016/J.BONE.2005.05.011.

    Article  CAS  PubMed  Google Scholar 

  20. Marriott, Ian, David L. Gray, Susanne L. Tranguch, Vance G. Fowler, Martin Stryjewski, L. Scott Levin, Michael C. Hudson, and Kenneth L. Bost. 2004. Osteoblasts express the inflammatory cytokine interleukin-6 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue. American Journal of Pathology 164. American Society for Investigative Pathology Inc.: 1399–1406. https://doi.org/10.1016/S0002-9440(10)63226-9.

  21. Marriott, Ian, Francis M. Hughes, and Kenneth L. Bost. 2002. Bacterial infection of osteoblasts induces interleukin-1β and interleukin-18 transcription but not protein synthesis. Journal of Interferon and Cytokine Research 22: 1049–1055. https://doi.org/10.1089/107999002760624288.

    Article  CAS  PubMed  Google Scholar 

  22. Marriott, Ian. 2004. Osteoblast responses to bacterial pathogens: A previously unappreciated role for bone-forming cells in host defense and disease progression. Immunologic Research 30: 291–308. https://doi.org/10.1385/IR:30:3:291.

    Article  CAS  PubMed  Google Scholar 

  23. Liu, Da., Lei Sheng Jiang, and Li Yang Dai. 2007. Substance P and its receptors in bone metabolism. Neuropeptides. https://doi.org/10.1016/j.npep.2007.05.003.

    Article  PubMed  Google Scholar 

  24. Niedermair, Tanja, Stephan Schirner, Raphael Seebröker, Rainer H. Straub, and Susanne Grässel. 2018. Substance P modulates bone remodeling properties of murine osteoblasts and osteoclasts. Scientific Reports 8. https://doi.org/10.1038/s41598-018-27432-y

  25. Xing, Li., Fu., Feng Xu Zi, Xiao Lin, Wu. Feng, Jia Yu Zhong, Yi. Wang, Bei Guo, Ming Hui Zheng, Su Kang Shan, and Ling Qing Yuan. 2020. The role of substance P in the regulation of bone and cartilage metabolic activity. Frontiers in Endocrinology. https://doi.org/10.3389/fendo.2020.00077.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Imai, Shinji, and Yoshitaka Matsusue. 2002. Neuronal regulation of bone metabolism and anabolism: calcitonin gene-related peptide-, substance P-, and tyrosine hydroxylase-containing nerves and the bone. Microscopy Research and Technique 58. https://doi.org/10.1002/jemt.10119

  27. Lerner, Ulf H. 2002. Neuropeptidergic regulation of bone resorption and bone formation. Journal of Musculoskeletal Neuronal Interactions 2.

  28. Goto, Tetsuya, Takayoshi Yamaza, Mizuho A. Kido, and Teruo Tanaka. 1998. Light- and electron-microscopic study of the distribution of axons containing substance P and the localization of neurokinin-1 receptor in bone. Cell and Tissue Research 293. https://doi.org/10.1007/s004410051100

  29. Grässel, Susanne. 2014. The role of peripheral nerve fibers and their neurotransmitters in cartilage and bone physiology and pathophysiology. Arthritis Research and Therapy. https://doi.org/10.1186/s13075-014-0485-1.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Sun, Seungyup, Nicklaus H. Diggins, Zachary J. Gunderson, Jill C. Fehrenbacher, Fletcher A. White, and Melissa A. Kacena. 2020. No pain, no gain? The effects of pain-promoting neuropeptides and neurotrophins on fracture healing. Bone 131. Elsevier Inc. https://doi.org/10.1016/J.BONE.2019.115109.

  31. Marriott, I., and K.L. Bost. 2001. Expression of authentic substance P receptors in murine and human dendritic cells. Journal of neuroimmunology 114: 131–141.

    Article  CAS  PubMed  Google Scholar 

  32. Burmeister, Amanda R., M. Brittany Johnson, Vinita S. Chauhan, Megan J. Moerdyk-Schauwecker, Ada D. Young, Ian D. Cooley, Alejandra N. Martinez, Geeta Ramesh, Mario T. Philipp, and Ian Marriott. 2017. Human microglia and astrocytes constitutively express the neurokinin-1 receptor and functionally respond to substance P. Journal of Neuroinflammation. https://doi.org/10.1186/s12974-017-1012-5.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Marriott, Ian, Michael J. Mason, Adam Elhofy, and Kenneth L. Bost. 2000. Substance P activates NF-κB independent of elevations in intracellular calcium in murine macrophages and dendritic cells. Journal of Neuroimmunology 102: 163–171. https://doi.org/10.1016/S0165-5728(99)00182-4.

    Article  CAS  PubMed  Google Scholar 

  34. Kataeva, G., A. Agro, and A.M. Stanisz. 1994. Substance-P-mediated intestinal inflammation: Inhibitory effects of CP 96,345 and SMS 201–995. NeuroImmunoModulation 1: 350–356. https://doi.org/10.1159/000097187.

    Article  CAS  PubMed  Google Scholar 

  35. Marriott, Ian, and Kenneth L. Bost. 2001. Substance P receptor mediated macrophage responses. In Neuroimmune Circuits, Drugs of Abuse, and Infectious Diseases, 493:247–254. Boston: Kluwer Academic Publishers. https://doi.org/10.1007/0-306-47611-8_30.

  36. Rogers, Donna P., Carol R. Wyatt, Paul H. Walz, James S. Drouillard, and Derek A. Mosier. 2006. Bovine alveolar macrophage neurokinin-1 and response to substance P. Veterinary Immunology and Immunopathology 112: 290–295. https://doi.org/10.1016/J.VETIMM.2006.03.001.

    Article  CAS  PubMed  Google Scholar 

  37. Rasley, Amy, Ian Marriott, Craig R Halberstadt, Kenneth L Bost, and Juan Anguita. 2004. Substance P augments Borrelia burgdorferi-induced prostaglandin E2 production by murine microglia. Journal of immunology (Baltimore, Md. : 1950) 172: 5707–13.

  38. Marriott, I., M.J. Mason, A. Elhofy, and K.L. Bost. 2000. Substance P activates NF-kappaB independent of elevations in intracellular calcium in murine macrophages and dendritic cells. Journal of neuroimmunology 102: 163–171.

    Article  CAS  PubMed  Google Scholar 

  39. Landau, A.M., K. Yashpal, C.M. Cahill, and M. st. Louis, A. Ribeiro-da-Silva, and J. L. Henry. 2007. Sensory neuron and substance P involvement in symptoms of a zymosan-induced rat model of acute bowel inflammation. Neuroscience 145: 699–707. https://doi.org/10.1016/J.NEUROSCIENCE.2006.11.066.

    Article  CAS  PubMed  Google Scholar 

  40. Elsawa, Sherine F, William Taylor, Cynthia C Petty, Ian Marriott, Joel v Weinstock, and Kenneth L Bost. 2003. Reduced CTL response and increased viral burden in substance P receptor-deficient mice infected with murine gamma-herpesvirus 68. Journal of immunology (Baltimore, Md. : 1950) 170: 2605–12.

  41. Wang, Liping, Rong Zhao, Xiaoyou Shi, Tzuping Wei, Bernard P. Halloran, David J. Clark, Christopher R. Jacobs, and Wade S. Kingery. 2009. Substance P stimulates bone marrow stromal cell osteogenic activity, osteoclast differentiation, and resorption activity in vitro. Bone 45: 309–320. https://doi.org/10.1016/J.BONE.2009.04.203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Vincent, Cristina, Masakazu Kogawa, David M. Findlay, and Gerald J. Atkins. 2009. The generation of osteoclasts from RAW 264.7 precursors in defined, serum-free conditions. Journal of Bone and Mineral Metabolism 27: 114–119. https://doi.org/10.1007/S00774-008-0018-6.

    Article  CAS  PubMed  Google Scholar 

  43. Ng, Andrew Y.H., Chengjian Tu, Shichen Shen, Ding Xu, Merry J. Oursler, Jun Qu, and Shuying Yang. 2018. Comparative characterization of osteoclasts derived from murine bone marrow macrophages and RAW 264.7 cells using quantitative proteomics. JBMR Plus 2. Blackwell Publishing Ltd: 328–340. https://doi.org/10.1002/JBM4.10058.

  44. Collin-Osdoby, Patricia, and Philip Osdoby. 2012. RANKL-mediated osteoclast formation from murine RAW 264.7 cells. Methods in Molecular Biology 816: 187–202. https://doi.org/10.1007/978-1-61779-415-5_13.

    Article  CAS  PubMed  Google Scholar 

  45. Bost, Kenneth L, Jennifer L Bento, Cynthia C Petty, Laura W Schrum, Michael C Hudson, and Ian Marriott. 2001. Monocyte chemoattractant protein-1 expression by osteoblasts following infection with Staphylococcus aureus or Salmonella. Journal of Interferon and Cytokine Research. 21. Mary Ann Liebert, Inc.

  46. Spagnolo, N., F. Greco, A. Rossi, L. Ciolli, A. Teti, and P. Posteraro. 1993. Chronic staphylococcal osteomyelitis: A new experimental rat model. Infection and Immunity 61: 5225–5230. https://doi.org/10.1128/IAI.61.12.5225-5230.1993.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Goto, Tetsuya, Takayoshi Yamaza, Mizuho A. Kido, and Teruo Tanaka. 2001. Substance P activates osteoclast formation and osteoclastic bene resorption through the neurokinin-1 receptor. Acta Histochemica et Cytochemica 34. https://doi.org/10.1267/ahc.34.31

  48. Sohn, Soo Joon. 2005. Substance P upregulates osteoclastogenesis by activating nuclear factor kappa B in osteoclast precursors. Acta Oto-Laryngologica 125. https://doi.org/10.1080/00016480410017710

  49. Sun, Ying Ming, Song Jiao Luo, and Yu Hui Zhao. 2006. Substance P regulates function of osteoclasts via neurokinin-1 receptor. Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology 24.

  50. Eiji Fukuhara Tetsuya Goto Takaaki Matayoshi Shigeru Kobayashi Tetsu Takahashi 2005 Substance P stimulates the formation of osteoclasts from human peripheral blood monocytes The Journal of the Kyushu Dental Society 59 https://doi.org/10.2504/kds.59.53

  51. Matayoshi, Takaaki, Tetsuya Goto, Eiji Fukuhara, Hiroshi Takano, Shigeru Kobayashi, and Tetsu Takahashi. 2005. Neuropeptide substance P stimulates the formation of osteoclasts via synovial fibroblastic cells. Biochemical and Biophysical Research Communications 327. https://doi.org/10.1016/j.bbrc.2004.12.05

  52. Krause, J. E., D. A. DiMaggio, and K. E. McCarson. 1995. Alterations in neurokinin 1 receptor gene expression in models of pain and inflammation. Canadian Journal of Physiology and Pharmacology 73. Canadian Science Publishing: 854–859. https://doi.org/10.1139/Y95-117.

  53. Liu, J.Y., J.H. Hu, Q.G. Zhu, F.Q. Li, and H.J. Sun. 2006. Substance P receptor expression in human skin keratinocytes and fibroblasts. British Journal of Dermatology 155: 657–662. https://doi.org/10.1111/J.1365-2133.2006.07408.X.

    Article  CAS  PubMed  Google Scholar 

  54. Bae, Sang Jae, Yoshitaka Matsunaga, Motoi Takenaka, Yoichi Tanaka, Yoichiro Hamazaki, Kazuhiro Shimizu, and Ichiro Katayama. 2002. Substance P induced preprotachykinin-A mRNA, neutral endopeptidase mRNA and substance P in cultured normal fibroblasts. International Archives of Allergy and Immunology 127: 316–321. https://doi.org/10.1159/000057749.

    Article  CAS  PubMed  Google Scholar 

  55. Heffner, Mollie A., Damian C. Genetos, and Blaine A. Christiansen. 2017. Bone adaptation to mechanical loading in a mouse model of reduced peripheral sensory nerve function. PLoS ONE 12. Public Library of Science. https://doi.org/10.1371/JOURNAL.PONE.0187354.

  56. Sun, Hai Biao, Jun Chang Chen, Qiang Liu, Min Feng Guo, and Hua Ping Zhang. 2010. Substance P stimulates differentiation of mice osteoblast through up-regulating Osterix expression. Chinese Journal of Traumatology - English Edition 13. Elsevier B.V.: 46–50. https://doi.org/10.3760/CMA.J.ISSN.1008-1275.2010.01.009.

  57. Salisbury, Elizabeth, Eric Rodenberg, Corinne Sonnet, John Hipp, Francis H. Gannon, Tegy J. Vadakkan, Mary E. Dickinson, Elizabeth A. Olmsted-Davis, and Alan R. Davis. 2011. Sensory nerve induced inflammation contributes to heterotopic ossification. Journal of Cellular Biochemistry 112: 2748–2758. https://doi.org/10.1002/JCB.23225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Azuma, Hideki, Jun-ichi Kido, Dai Ikedo, Masatoshi Kataoka, and Toshihiko Nagata. 2004. Substance P enhances the inhibition of osteoblastic cell differentiation induced by lipopolysaccharide from Porphyromonas gingivalis . Journal of Periodontology 75. Wiley: 974–981. https://doi.org/10.1902/JOP.2004.75.7.974.

  59. Yamaza, Takayoshi, Mizuho A. Kido, Bing Wang, Atsushi Danjo, Daiji Shimohira, Naohisa Murata, Masao Yoshinari, and Teruo Tanaka. 2009. Distribution of substance P and neurokinin-1 receptors in the peri-implant epithelium around titanium dental implants in rats. Cell and Tissue Research 335: 407–415. https://doi.org/10.1007/S00441-008-0720-7.

    Article  CAS  PubMed  Google Scholar 

  60. Chauhan, Vinita S., John M. Kluttz, Kenneth L. Bost, and Ian Marriott. 2011. Prophylactic and therapeutic targeting of the neurokinin-1 receptor limits neuroinflammation in a murine model of pneumococcal meningitis. The Journal of Immunology 186. The American Association of Immunologists: 7255–7263. https://doi.org/10.4049/JIMMUNOL.1100721.

  61. Chauhan, Vinita S, David G Sterka, David L Gray, Kenneth L Bost, and Ian Marriott. 2008. Neurogenic exacerbation of microglial and astrocyte responses to Neisseria meningitidis and Borrelia burgdorferi. Journal of Immunology (Baltimore, Md. : 1950) 180: 8241–9.

  62. Marriott, I, and K L Bost. 2000. IL-4 and IFN-gamma up-regulate substance P receptor expression in murine peritoneal macrophages. Journal of Immunology (Baltimore, Md. : 1950) 165: 182–91.

  63. Grady, Eileen F., Shandra K. Yoshimi, John Maa, Dahlia Valeroso, Robert K. Vartanian, Shamila Rahim, Edward H. Kim, et al. 2000. Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice. British Journal of Pharmacology 130. John Wiley and Sons Inc.: 505–512. https://doi.org/10.1038/SJ.BJP.0703343.

  64. Hayashida, Chiyomi, Junta Ito, Mai Nakayachi, Mari Okayasu, Yoko Ohyama, Yoshiyuki Hakeda, and Takuya Sato. 2014. Osteocytes produce interferon-β as a negative regulator of osteoclastogenesis. Journal of Biological Chemistry 289. American Society for Biochemistry and Molecular Biology Inc.: 11545–11555. https://doi.org/10.1074/JBC.M113.523811.

  65. Zhao, Rong, Ni Nan Chen, Xiao Wei Zhou, Ping Miao, Chao Ying Hu, Liu Qian, Qi Wen Yu, et al. 2014. Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model. Journal of Translational Medicine 12. BioMed Central Ltd. https://doi.org/10.1186/S12967-014-0330-Y.

  66. Nakamura, Takahiro, Toshio Kukita, Takeo Shobuike, Kengo Nagata, Zhou Wu, Kenji Ogawa, Takao Hotokebuchi, Osamu Kohashi, and Akiko Kukita. 2005. Inhibition of histone deacetylase suppresses osteoclastogenesis and bone destruction by inducing IFN-β production. The Journal of Immunology 175. The American Association of Immunologists: 5809–5816. https://doi.org/10.4049/JIMMUNOL.175.9.5809.

  67. Takayanagi, Hiroshi, Sunhwa Kim, and Tadatsugu Taniguchi. 2002. Signaling crosstalk between RANKL and interferons in osteoclast differentiation. Arthritis research 4: S227–S232. https://doi.org/10.1186/AR581.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Place, David E., R. K.Subbarao Malireddi, Jieun Kim, Peter Vogel, Masahiro Yamamoto, and Thirumala Devi Kanneganti. 2021. Osteoclast fusion and bone loss are restricted by interferon inducible guanylate binding proteins. Nature Communications 12. Nature Research. https://doi.org/10.1038/S41467-020-20807-8.

  69. Zheng, Hong, Yu. Xuefeng, Patricia Collin-Osdoby, and Philip Osdoby. 2006. RANKL stimulates inducible nitric-oxide synthase expression and nitric oxide production in developing osteoclasts: An autocrine negative feedback mechanism triggered by RANKL-induced interferon-β via NF-κB that restrains osteoclastogenesis and bone resorption. Journal of Biological Chemistry 281: 15809–15820. https://doi.org/10.1074/JBC.M513225200.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by grant AR074102 to IM from the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC, 28223, USA

    M. Brittany Johnson, Samantha R. Suptela, Sophie E. Sipprell & Ian Marriott

Authors
  1. M. Brittany Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samantha R. Suptela
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sophie E. Sipprell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ian Marriott
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MBJ, SRS, and SES harvested primary murine osteoblasts and bone marrow and performed in vivo bone infections in mice, in accordance with approved IACUC protocols; prepared bacterial stocks; carried out the in vitro experiments, specific capture ELISAs, and immunoblot analyses; and performed data analysis. IM conceived the study, contributed to the experimental design, and drafted the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Ian Marriott.

Ethics declarations

Ethics Approval

All protocols involving animals were approved by the Institutional Animal Care and Use Committee of the University of North Carolina at Charlotte.

Consent to Participate

These studies did not involve human subjects.

Consent for Publication

These studies did not involve human subjects.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 3759 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Johnson, M.B., Suptela, S.R., Sipprell, S.E. et al. Substance P Exacerbates the Inflammatory and Pro-osteoclastogenic Responses of Murine Osteoclasts and Osteoblasts to Staphylococcus aureus. Inflammation 46, 256–269 (2023). https://doi.org/10.1007/s10753-022-01731-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-022-01731-z

KEY WORDS

Search

Navigation