Human osteocyte expression of Nerve Growth Factor: The effect of Pentosan Polysulphate Sodium (PPS) and implications for pain associated with knee osteoarthritis


Autoři: Catherine J. M. Stapledon aff001;  Helen Tsangari aff001;  Lucian B. Solomon aff001;  David G. Campbell aff001;  Plinio Hurtado aff004;  Ravi Krishnan aff005;  Gerald J. Atkins aff001
Působiště autorů: Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, South Australia, Australia aff001;  Orthopaedic and Trauma Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia aff002;  Wakefield Orthopaedic Clinic, Calvary Wakefield Hospital, Adelaide, South Australia, Australia aff003;  Renal Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia aff004;  Paradigm Biopharmaceuticals Ltd., Melbourne, Victoria, Australia aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222602

Souhrn

Pentosan polysulphate sodium (PPS) is a promising therapeutic agent for blocking knee pain in individuals with knee osteoarthritis (KOA). The mode of action of PPS in this context is unknown. We hypothesised that the osteocyte, being the principal cell type in the sub-chondral bone, was capable of expressing the pain mediator Nerve Growth Factor (NGF), and that this may be altered in the presence of PPS. We tested the expression of NGF and the response to PPS in the presence or absence of the proinflammatory cytokine tumour necrosis factor-alpha (TNFα), in human osteocytes. For this we differentiated human primary osteoblasts grown from subchondral bone obtained at primary knee arthroplasty for KOA to an osteocyte-like stage over 28d. We also tested NGF expression in fresh osteocytes obtained by sequential digestion from KOA bone and by immunofluorescence in KOA bone sections. We demonstrate for the first time the production and secretion of NGF/proNGF by this cell type derived from patients with KOA, implicating osteocytes in the pain response in this pathological condition and possibly others. PPS inhibited TNFα-induced levels of proNGF secretion and TNFα induced NGF mRNA expression. Together, this provides evidence that PPS may act to suppress the release of NGF in the subchondral bone to ameliorate pain associated with knee osteoarthritis.

Klíčová slova:

Enzyme-linked immunoassays – Gene expression – Knees – Osteoarthritis – Secretion – Osteocytes – Immunostaining – Osteoblast differentiation


Zdroje

1. Chevalier X, Eymard F, Richette P. Biologic agents in osteoarthritis: hopes and disappointments. Nat Rev Rheumatol. 2013;9(7):400–10. Epub 2013/04/03. doi: 10.1038/nrrheum.2013.44 23545735.

2. Ayers DC, Li W, Harrold L, Allison J, Franklin PD. Preoperative pain and function profiles reflect consistent TKA patient selection among US surgeons. Clin Orthop Relat Res. 2015;473(1):76–81. Epub 2014/06/25. doi: 10.1007/s11999-014-3716-5 24957788; PubMed Central PMCID: PMC4390921.

3. Tomlinson RE, Li Z, Li Z, Minichiello L, Riddle RC, Venkatesan A, et al. NGF-TrkA signaling in sensory nerves is required for skeletal adaptation to mechanical loads in mice. Proc Natl Acad Sci U S A. 2017;114(18):E3632–E41. Epub 2017/04/19. doi: 10.1073/pnas.1701054114 28416686; PubMed Central PMCID: PMC5422802.

4. Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shelton DL, Smith MD, et al. Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med. 2010;363(16):1521–31. Epub 2010/10/15. doi: 10.1056/NEJMoa0901510 20942668.

5. Schnitzer TJ, Ekman EF, Spierings EL, Greenberg HS, Smith MD, Brown MT, et al. Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain. Ann Rheum Dis. 2015;74(6):1202–11. Epub 2014/03/15. doi: 10.1136/annrheumdis-2013-204905 24625625.

6. Ekman EF, Gimbel JS, Bello AE, Smith MD, Keller DS, Annis KM, et al. Efficacy and safety of intravenous tanezumab for the symptomatic treatment of osteoarthritis: 2 randomized controlled trials versus naproxen. J Rheumatol. 2014;41(11):2249–59. Epub 2014/10/03. doi: 10.3899/jrheum.131294 25274899.

7. Takano S, Uchida K, Miyagi M, Inoue G, Fujimaki H, Aikawa J, et al. Nerve Growth Factor Regulation by TNF-alpha and IL-1beta in Synovial Macrophages and Fibroblasts in Osteoarthritic Mice. J Immunol Res. 2016;2016:5706359. Epub 2016/09/17. doi: 10.1155/2016/5706359 27635406; PubMed Central PMCID: PMC5007361.

8. Bradshaw RA, Pundavela J, Biarc J, Chalkley RJ, Burlingame AL, Hondermarck H. NGF and ProNGF: Regulation of neuronal and neoplastic responses through receptor signaling. Adv Biol Regul. 2015;58:16–27. Epub 2014/12/11. doi: 10.1016/j.jbior.2014.11.003 25491371; PubMed Central PMCID: PMC4426037.

9. Malerba F, Paoletti F, Cattaneo A. NGF and proNGF Reciprocal Interference in Immunoassays: Open Questions, Criticalities, and Ways Forward. Front Mol Neurosci. 2016;9:63. Epub 2016/08/19. doi: 10.3389/fnmol.2016.00063 27536217; PubMed Central PMCID: PMC4971159.

10. Giusto LL, Zahner PM, Shoskes DA. An evaluation of the pharmacotherapy for interstitial cystitis. Expert Opin Pharmacother. 2018;19(10):1097–108. Epub 2018/07/05. doi: 10.1080/14656566.2018.1491968 29972328.

11. Sampson MJ, Kabbani M, Krishnan R, Nganga M, Theodoulou A, Krishnan J. Improved clinical outcome measures of knee pain and function with concurrent resolution of subchondral Bone Marrow Edema Lesion and joint effusion in an osteoarthritic patient following Pentosan Polysulphate Sodium treatment: a case report. BMC Musculoskelet Disord. 2017;18(1):396. Epub 2017/09/14. doi: 10.1186/s12891-017-1754-3 28899386; PubMed Central PMCID: PMC5596862.

12. Kumagai K, Shirabe S, Miyata N, Murata M, Yamauchi A, Kataoka Y, et al. Sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis—an open clinical trial. (1472–6904 (Electronic)).

13. Sunaga T, Oh N, Hosoya K, Takagi S, Okumura M. Inhibitory effects of pentosan polysulfate sodium on MAP-kinase pathway and NF-kappaB nuclear translocation in canine chondrocytes in vitro. The Journal of veterinary medical science / the Japanese Society of Veterinary Science. 2012;74(6):707–11. Epub 2012/01/05. doi: 10.1292/jvms.11-0511 22214865.

14. Bwalya EC, Kim S, Fang J, Wijekoon HMS, Hosoya K, Okumura M. Pentosan polysulfate inhibits IL-1beta-induced iNOS, c-Jun and HIF-1alpha upregulation in canine articular chondrocytes. PLoS One. 2017;12(5):e0177144. Epub 2017/05/05. doi: 10.1371/journal.pone.0177144 28472120; PubMed Central PMCID: PMC5417682.

15. Atkins GJ, Findlay DM. Osteocyte regulation of bone mineral: a little give and take. Osteoporos Int. 2012;23(8):2067–79. Epub 2012/02/04. doi: 10.1007/s00198-012-1915-z 22302104.

16. Prideaux M, Findlay DM, Atkins GJ. Osteocytes: The master cells in bone remodelling. Curr Opin Pharmacol. 2016;28:24–30. doi: 10.1016/j.coph.2016.02.003 26927500.

17. Ormsby RT, Cantley M, Kogawa M, Solomon LB, Haynes DR, Findlay DM, et al. Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis. Acta Biomater. 2016;33:242–51. Epub 2016/01/23. doi: 10.1016/j.actbio.2016.01.016 26796208.

18. Yang D, Wijenayaka AR, Solomon LB, Pederson SM, Findlay DM, Kidd SP, et al. Novel Insights into Staphylococcus aureus Deep Bone Infections: the Involvement of Osteocytes. MBio. 2018;9(2). Epub 2018/04/25. doi: 10.1128/mBio.00415-18 29691335; PubMed Central PMCID: PMC5915738.

19. Atkins GJ, Rowe PS, Lim HP, Welldon KJ, Ormsby R, Wijenayaka AR, et al. Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism. J Bone Miner Res. 2011;26(7):1425–36. Epub 2011/02/12. doi: 10.1002/jbmr.345 21312267; PubMed Central PMCID: PMC3358926.

20. Atkins GJ, Welldon KJ, Wijenayaka AR, Bonewald LF, Findlay DM. Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by {gamma}-carboxylation-dependent and -independent mechanisms. Am J Physiol Cell Physiol. 2009;297(6):C1358–67. Epub 2009/08/14. doi: 10.1152/ajpcell.00216.2009 19675304.

21. Kogawa M, Wijenayaka AR, Ormsby RT, Thomas GP, Anderson PH, Bonewald LF, et al. Sclerostin Regulates Release of Bone Mineral by Osteocytes by Induction of Carbonic Anhydrase 2. J Bone Miner Res. 2013;28(12):2436–48. Epub 2013/06/06. doi: 10.1002/jbmr.2003 23737439.

22. Kumarasinghe DD, Sullivan T, Kuliwaba JS, Fazzalari NL, Atkins GJ. Evidence for the dysregulated expression of TWIST1, TGFβ1 and SMAD3 in differentiating osteoblasts from primary hip osteoarthritis patients. Osteoarthritis & Cartilage. 2012;20:1357–66.

23. Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One. 2011;6(10):e25900. doi: 10.1371/journal.pone.0025900 21991382; PubMed Central PMCID: PMC3186800.

24. Ghosh P, Wu J, Shimmon S, Zannettino AC, Gronthos S, Itescu S. Pentosan polysulfate promotes proliferation and chondrogenic differentiation of adult human bone marrow-derived mesenchymal precursor cells. Arthritis Res Ther. 2010;12(1):R28. Epub 2010/02/20. doi: 10.1186/ar2935 20167057; PubMed Central PMCID: PMC2875662.

25. Prideaux M, Schutz C, Wijenayaka AR, Findlay DM, Campbell DG, Solomon LB, et al. Isolation of osteocytes from human trabecular bone. Bone. 2016;88:64–72. Epub 2016/04/26. doi: 10.1016/j.bone.2016.04.017 27109824.

26. Iannone F, De Bari C, Dell'Accio F, Covelli M, Patella V, Lo Bianco G, et al. Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes. Rheumatology (Oxford). 2002;41(12):1413–8. Epub 2002/12/07. doi: 10.1093/rheumatology/41.12.1413 12468822.

27. Zhang J, Wang LS, Ye SL, Luo P, Wang BL. Blockage of tropomyosin receptor kinase a (TrkA) enhances chemo-sensitivity in breast cancer cells and inhibits metastasis in vivo. Int J Clin Exp Med. 2015;8(1):634–41. Epub 2015/03/19. doi: Not available. 25785038; PubMed Central PMCID: PMC4358493.

28. Rouillard AD, Gundersen GW, Fernandez NF, Wang Z, Monteiro CD, McDermott MG, et al. The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. LID—10.1093/database/baw100 [doi] LID—baw100 [pii]. (1758–0463 (Electronic)).

29. Atkins GJ, Welldon KJ, Halbout P, Findlay DM. Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. Osteoporos Int. 2009;20(4):653–64. doi: 10.1007/s00198-008-0728-6 18763010.

30. Bonewald LF. The amazing osteocyte. J Bone Miner Res. 2011;26(2):229–38. Epub 2011/01/22. doi: 10.1002/jbmr.320 21254230.

31. Manni L, Aloe L. Role of IL-1 beta and TNF-alpha in the regulation of NGF in experimentally induced arthritis in mice. Rheumatol Int. 1998;18(3):97–102. Epub 1998/12/02. 9833249.

32. Dawes J Fau— Prowse CV, Prowse Cv Fau— Pepper DS, Pepper DS. Absorption of heparin, LMW heparin and SP54 after subcutaneous injection, assessed by competitive binding assay. Thrombosis Research. 1986;44(0049–3848 (Print)):683–93. doi: 10.1016/0049-3848(86)90169-6 2433788

33. Castaneda-Corral G, Jimenez-Andrade JM, Bloom AP, Taylor RN, Mantyh WG, Kaczmarska MJ, et al. The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A. Neuroscience. 2011;178:196–207. Epub 2011/02/01. doi: 10.1016/j.neuroscience.2011.01.039 21277945; PubMed Central PMCID: PMC3078085.


Článek vyšel v časopise

PLOS One


2019 Číslo 9
Nejčtenější tento týden