Abstract
Objectives
We employed the co-culture of CD34+ stem cell-derived human mast cells (HMC) and human monocyte-derived osteoclast precursors to evaluate if mast cells contribute to the pathogenesis of osteoporosis through regulation of osteoclast proliferation and activation.
Methods
Mature HMC and osteoclast precursors were cultured from monocytes isolated from human buffy coat. The osteoclast precursors were incubated with HMC or receptor activator of nuclear factor kappa-B ligand (RANKL) for a week prior to determination of osteoclast maturation through characterization by their morphology and tartrate resistant acid phosphatase (TRAP) expression. The bone absorption activity was determined by pit formation on osteo-assay plate.
Results
Mature osteoclasts were identified following co-culture of osteoclast precursors with HMC for one week in the absence of RANKL and they were capable of bone resorption. These actions of HMC on osteoclasts were not affected by mast cell activators such anti-IgE or substance P but could be reversed by osteoprotegerin (OPG) in the co-culture system suggesting the involvement of RANKL. The expression of RANKL on the cell surface of HMC was confirmed by flow cytometry and the density was not affected by activation of HMC.
Conclusion
Our study provided direct evidence confirming the initiation of osteoclast proliferation and activation by mast cells through cell surface RANKL suggesting that mast cells may contribute to bone destruction in pathological conditions such as osteoporosis.
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References
Drake MT, Clarke BL, Lewiecki EM. The pathophysiology and treatment of osteoporosis. Clin Ther. 2015;37:1837–50.
Datta HK, Ng WF, Walker JA, Tuck SP, Varanasi SS. The cell biology of bone metabolism. J Clin Pathol. 2008;61:577–87.
Krishnaswamy G, Kelley J, Johnson D, Youngberg G, Stone W, Huang SK, et al. The human mast cell: functions in physiology and disease. Front Biosci. 2001;6:D1109–27.
Chiappetta N, Gruber B. The role of mast cells in osteoporosis. Semin Arthritis Rheum. 2006;36:32–6.
Ragipoglu D, Dudeck A, Haffner-Luntzer M, Voss M, Kroner J, Ignatius A, et al. The role of mast cells in bone metabolism and bone disorders. Front Immunol. 2020;11:163.
Ali AS, Lax AS, Liljestrom M, Paakkari I, Ashammakhi N, Kovanen PT, et al. Mast cells in atherosclerosis as a source of the cytokine RANKL. Clin Chem Lab Med. 2006;44:672–4.
Kroner J, Kovtun A, Kemmler J, Messmann JJ, Strauss G, Seitz S, et al. Mast cells are critical regulators of bone fracture-induced inflammation and osteoclast formation and activity. J Bone Miner Res. 2017;32:2431–44.
Urist MR, McLean FC. Accumulation of mast cells in endosteum of bones of calcium-deficient rats. AMA Arch Pathol. 1957;63:239–51.
Fallon MD, Whyte MP, Craig RB Jr, Teitelbaum SL. Mast-cell proliferation in postmenopausal osteoporosis. Calcif Tissue Int. 1983;35:29–31.
Lesclous P, Guez D, Llorens A, Saffar JL. Time-course of mast cell accumulation in rat bone marrow after ovariectomy. Calcif Tissue Int. 2001;68:297–303.
Chan BC, Lee HY, Siu WS, Yip KH, Ko CH, Lau CB, et al. Suppression of mast cell activity contributes to the osteoprotective effect of an herbal formula containing Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae. J Pharm Pharmacol. 2014;66:437–44.
Drudy L, Sheppard BL, Bonnar J. The mast cell and histamine concentration of the human post-menopausal uterus. Eur J Obstet Gynecol Reprod Biol. 1991;42:39–42.
Lesclous P, Saffar JL. Mast cells accumulate in rat bone marrow after ovariectomy. Cells Tissues Organs. 1999;164:23–9.
Biosse-Duplan M, Baroukh B, Dy M, de Vernejoul MC, Saffar JL. Histamine promotes osteoclastogenesis through the differential expression of histamine receptors on osteoclasts and osteoblasts. Am J Pathol. 2009;174:1426–34.
Tam IYS, Ng CW, Tam SY, Lau HYA. Novel six-week protocol for generating functional human connective tissue-type (MCTC) mast cells from buffy coats. Inflamm Res. 2017;66:25–37.
Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5.
Costa-Rodrigues J, Fernandes A, Fernandes MH. Spontaneous and induced osteoclastogenic behaviour of human peripheral blood mononuclear cells and their CD14(+) and CD14(-) cell fractions. Cell Prolif. 2011;44:410–9.
Fouilloux I, Duplan MB, Baroukh B, Cherruau M, Saffar JL, Lesclous P. Mast cell activation and degranulation occur early during induction of periosteal bone resorption. Bone. 2006;38:59–66.
McKenna MJ, Frame B. The mast cell and bone. Clin Orthop Relat Res. 1985;200:226–33.
Orsolini G, Gavioli I, Tripi G, Viapiana O, Gatti D, Idolazzi L, et al. Denosumab for the treatment of mastocytosis-related osteoporosis: a case series. Calcif Tissue Int. 2017;100:595–8.
Findlay DM, Atkins GJ. Relationship between serum RANKL and RANKL in bone. Osteoporos Int. 2011;22:2597–602.
Elango J, Bao B, Wu W. The hidden secrets of soluble RANKL in bone biology. Cytokine. 2021;144: 155559.
Lum L, Wong BR, Josien R, Becherer JD, Erdjument-Bromage H, Schlondorff J, et al. Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival. J Biol Chem. 1999;274:13613–8.
Turner RT, Iwaniec UT, Marley K, Sibonga JD. The role of mast cells in parathyroid bone disease. J Bone Miner Res. 2010;25:1637–49.
Funding
This study was supported by the Research Fund for the Control of Infectious Diseases, Food and Health Bureau, Hong Kong SAR Government (ref no. 12130461).
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Study design: BC, CK, CL,PL and HL. Data acquisition: CN, IT and SS. Data analysis: CN, IT and HL. Drafting of manuscript: CN, IT and HL. All authors contributed to manuscript revision and approved the final version of the submitted manuscript.
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None of the authors have any conflict of interest, nor have they received any money for this study. Research is part of their daily activities. All authors had full access to all data and take responsibility for the integrity and accuracy of the data analysis.
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Ng, C.W., Chan, B.C.L., Ko, C.H. et al. Human mast cells induce osteoclastogenesis through cell surface RANKL. Inflamm. Res. 71, 1261–1270 (2022). https://doi.org/10.1007/s00011-022-01608-9
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DOI: https://doi.org/10.1007/s00011-022-01608-9