{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:48:17Z","timestamp":1793908097443,"version":"4.8.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR067748"],"award-info":[{"award-number":["R01AR067748"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR067748"],"award-info":[{"award-number":["R01AR067748"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Synovial macrophages perform a multitude of functions that include clearance of cell debris and foreign bodies, tissue immune surveillance, and resolution of inflammation. The functional diversity of macrophages is enabled by distinct subpopulations that express unique surface markers. Proteoglycan-4 (PRG4) is an important regulator of synovial hyperplasia and fibrotic remodeling, and the involvement of macrophages in PRG4\u2019s synovial role is yet to be defined. Our objectives were to study the PRG4\u2019s importance to macrophage homeostatic regulation in the synovium and infiltration of pro-inflammatory macrophages in acute synovitis and investigate whether macrophages mediated synovial fibrosis in\n                      <jats:italic>Prg4<\/jats:italic>\n                      gene-trap (\n                      <jats:italic>Prg4<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>GT\/GT<\/jats:italic>\n                      <\/jats:sup>\n                      ) murine knee joints.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Macrophage phenotyping in\n                      <jats:italic>Prg4<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>GT\/GT<\/jats:italic>\n                      <\/jats:sup>\n                      and\n                      <jats:italic>Prg4<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+\/+<\/jats:italic>\n                      <\/jats:sup>\n                      joints was performed by flow cytometry using pan-macrophage markers, e.g., CD11b, F4\/80, and surface markers of M1 macrophages (CD86) and M2 macrophages (CD206). Characterizations of the various macrophage subpopulations were performed in 2- and 6-month-old animals. The expression of inflammatory markers, IL-6, and iNOS in macrophages that are CD86+ and\/or CD206+ was studied. The impact of\n                      <jats:italic>Prg4<\/jats:italic>\n                      recombination on synovial macrophage populations of 2- and 6-month-old animals and infiltration of pro-inflammatory macrophages in response to a TLR2 agonist challenge was determined. Macrophages were depleted using liposomal clodronate and synovial membrane thickness, and the expression of fibrotic markers \u03b1-SMA, PLOD2, and collagen type I (COL-I) was assessed using immunohistochemistry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Total macrophages in\n                      <jats:italic>Prg4<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>GT\/GT<\/jats:italic>\n                      <\/jats:sup>\n                      joints were higher than\n                      <jats:italic>Prg4<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+\/+<\/jats:italic>\n                      <\/jats:sup>\n                      joints (\n                      <jats:italic>p&lt;0.0001<\/jats:italic>\n                      ) at 2 and 6 months, and the percentages of CD86+\/CD206\u2212 and CD86+\/CD206+ macrophages increased in\n                      <jats:italic>Prg4<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>GT<\/jats:italic>\n                        \/GT\n                      <\/jats:sup>\n                      joints at 6 months (\n                      <jats:italic>p&lt;0.0001<\/jats:italic>\n                      ), whereas the percentage of CD86\u2212\/CD206+ macrophages decreased (\n                      <jats:italic>p&lt;0.001<\/jats:italic>\n                      ). CD86+\/CD206\u2212 and CD86+\/CD206+ macrophages expressed iNOS and IL-6 compared to CD86\u2212\/CD206+ macrophages (\n                      <jats:italic>p&lt;0.0001<\/jats:italic>\n                      ).\n                      <jats:italic>Prg4<\/jats:italic>\n                      re-expression limited the accumulation of CD86+ macrophages (\n                      <jats:italic>p&lt;0.05<\/jats:italic>\n                      ) and increased CD86\u2212\/CD206+ macrophages (\n                      <jats:italic>p&lt;0.001<\/jats:italic>\n                      ) at 6 months.\n                      <jats:italic>Prg4<\/jats:italic>\n                      recombination attenuated synovial recruitment of pro-inflammatory macrophages in 2-month-old animals (\n                      <jats:italic>p&lt;0.001<\/jats:italic>\n                      ). Clodronate-mediated macrophage depletion reduced synovial hyperplasia, \u03b1-SMA, PLOD2, and COL-I expressions in the synovium (\n                      <jats:italic>p&lt;0.0001<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      PRG4 regulates the accumulation and homeostatic balance of macrophages in the synovium. In its absence, the synovium becomes populated with M1 macrophages. Furthermore, macrophages exert an effector role in synovial fibrosis in\n                      <jats:italic>Prg4<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>GT\/GT<\/jats:italic>\n                      <\/jats:sup>\n                      animals\n                      <jats:italic>.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-021-02621-9","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T04:03:14Z","timestamp":1631592194000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Proteoglycan-4 is an essential regulator of synovial macrophage polarization and inflammatory macrophage joint infiltration"],"prefix":"10.1186","volume":"23","author":[{"given":"Marwa","family":"Qadri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Jay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling X.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tannin A.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Totonchy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8925-4255","authenticated-orcid":false,"given":"Khaled A.","family":"Elsaid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"2621_CR1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.2174\/1874312901105010100","volume":"5","author":"MD Smith","year":"2011","unstructured":"Smith MD. The normal synovium. Open Rheumatol J. 2011;5:100\u20136.","journal-title":"Open Rheumatol J."},{"key":"2621_CR2","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1136\/ard.62.4.303","volume":"62","author":"MD Smith","year":"2003","unstructured":"Smith MD, Barg E, Weedon H, Papengellis V, Smeets T, Tak P, et al. Microarchitecture and protective mechanisms in synovial tissue from clinically and arthroscopically normal knee joints. Ann Rheum Dis. 2003;62:303\u20137.","journal-title":"Ann Rheum Dis."},{"issue":"4","key":"2621_CR3","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1111\/imm.12451","volume":"144","author":"LC Davies","year":"2015","unstructured":"Davies LC, Taylor PR. Tissue-resident macrophages: then and now. Immunology. 2015;144(4):541\u20138.","journal-title":"Immunology."},{"issue":"10","key":"2621_CR4","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/ni.2705","volume":"14","author":"LC Davies","year":"2013","unstructured":"Davies LC, Jenkin SJ, Allen JE, Taylor PR. Tissue-resident macrophages. Nat Immunol. 2013;14(10):986\u201395.","journal-title":"Nat Immunol."},{"issue":"7771","key":"2621_CR5","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1038\/s41586-019-1471-1","volume":"572","author":"S Culemann","year":"2019","unstructured":"Culemann S, Gr\u00fcneboom A, Nicolas-Avila JA, Weidner D, Lammie KF, Rothe T, et al. Locally renewing resident synovial macrophages provide a protective barrier for the joint. Nature. 2019;572(7771):670\u20135.","journal-title":"Nature."},{"issue":"3","key":"2621_CR6","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1002\/art.27290","volume":"62","author":"J Bondeson","year":"2010","unstructured":"Bondeson J, Blom AB, Wainwright S, Hughes C, Caterson B, van den Berg WB. The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis. Arthritis Rheum. 2010;62(3):647\u201357.","journal-title":"Arthritis Rheum."},{"issue":"9","key":"2621_CR7","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1016\/j.joca.2016.04.010","volume":"24","author":"VB Kraus","year":"2016","unstructured":"Kraus VB, McDaniel G, Huebner JL, Stabler TV, Pieper CF, Shipes SW, et al. Direct in vivo evidence of activated macrophages in human osteoarthritis. Osteoarthritis Cartilage. 2016;24(9):1613\u201321.","journal-title":"Osteoarthritis Cartilage."},{"key":"2621_CR8","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3389\/fimmu.2011.00052","volume":"2","author":"A Kennedy","year":"2011","unstructured":"Kennedy A, Fearson U, Veale DJ, Godson C. Macrophages in synovial inflammation. Front Immunol. 2011;2:52.","journal-title":"Front Immunol."},{"key":"2621_CR9","first-page":"1","volume":"5","author":"N Wang","year":"2014","unstructured":"Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage M1-M2 polarization balance. Fron Immunol. 2014;5:1\u20139.","journal-title":"Fron Immunol."},{"key":"2621_CR10","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.4049\/jimmunol.1701135","volume":"199","author":"K Ley","year":"2017","unstructured":"Ley K. M1 means kill; M2 means heal. J Immunol. 2017;199:2191\u20133.","journal-title":"J Immunol."},{"issue":"5","key":"2621_CR11","doi-asserted-by":"publisher","first-page":"23773","DOI":"10.4049\/jimmunol.1400486","volume":"193","author":"LT Donlin","year":"2014","unstructured":"Donlin LT, Jayatilleke A, Giannopoulou EG, Kalliolias GD, Ivashkiv LB. Modulation of TNF-induced macrophage polarization by synovial fibroblasts. J Immunol. 2014;193(5):23773\u20132383.","journal-title":"J Immunol."},{"issue":"10","key":"2621_CR12","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1136\/annrheumdis-2018-213450","volume":"77","author":"H Zhang","year":"2018","unstructured":"Zhang H, Lin C, Zeng C, Wang Z, Wang H, Lu J, et al. Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2. Ann Rheum Dis. 2018;77(10):1524\u201334.","journal-title":"Ann Rheum Dis."},{"key":"2621_CR13","doi-asserted-by":"crossref","unstructured":"Orecchioni M, Ghosheh Y, Pramond AB, Ley K. Macrophage polarization: different gene signatures in M1 (LPS+) vs. classically and M2 (LPS-) vs. alternatively activated macrophages. Front Immunol. 2019;10:1084.","DOI":"10.3389\/fimmu.2019.01084"},{"issue":"9","key":"2621_CR14","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1002\/art.40151","volume":"69","author":"QQ Huang","year":"2017","unstructured":"Huang QQ, Birkett R, Doyle RE, Haines GK, Perlman H, Shi B, et al. Association of increased F4\/80high macrophages with suppression of serum-transfer arthritis in mice with reduced FLIP in myeloid cells. Arthritis Rheumatol. 2017;69(9):1762\u201371.","journal-title":"Arthritis Rheumatol."},{"issue":"2","key":"2621_CR15","doi-asserted-by":"publisher","first-page":"R74","DOI":"10.1186\/ar3796","volume":"14","author":"CA Ambarus","year":"2012","unstructured":"Ambarus CA, Noordenbos T, de Hair MJ, Tak PP, Baeten DL. Intimal lining layer macrophages but not synovial sublining macrophages display an IL-10 polarized-like phenotype in chronic synovitis. Arthritis Res Ther. 2012;14(2):R74.","journal-title":"Arthritis Res Ther."},{"issue":"3","key":"2621_CR16","first-page":"594","volume":"27","author":"GD Jay","year":"2000","unstructured":"Jay GD, Britt DE, Cha CJ. Lubricin is a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts. J Rheumatol. 2000;27(3):594\u2013600.","journal-title":"J Rheumatol."},{"key":"2621_CR17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.matbio.2014.08.008","volume":"39","author":"GD Jay","year":"2014","unstructured":"Jay GD, Waller KA. The biology of lubricin: near frictionless joint motion. Matrix Biol. 2014;39:17\u201324.","journal-title":"Matrix Biol."},{"key":"2621_CR18","doi-asserted-by":"crossref","unstructured":"Waller KA, Zhang LX, Jay GD. Friction-induced mitochondrial dysregulation contributes to joint deterioration in Prg4 knockout mice. Int J Mol Sci. 2017;18(6).pii:E1252.","DOI":"10.3390\/ijms18061252"},{"issue":"6","key":"2621_CR19","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1002\/art.39087","volume":"67","author":"A Al-Sharif","year":"2015","unstructured":"Al-Sharif A, Jamal M, Zhang LX, Larson K, Schmidt TA, Elsaid KA. Lubricin\/proteoglycan 4 binding to CD44 receptor: a mechanism of the suppression of proinflammatory cytokine-induced synoviocyte proliferation by lubricin. Arthritis Rheumatol. 2015;67(6):1503\u201313.","journal-title":"Arthritis Rheumatol."},{"key":"2621_CR20","doi-asserted-by":"publisher","first-page":"18910","DOI":"10.1038\/srep18910","volume":"6","author":"SM Iqbal","year":"2016","unstructured":"Iqbal SM, Leonard C, Regmi SC, De Rantere D, Tailor P, Ren G, et al. Lubricin\/Proteoglycan 4 binds and regulates the activity of Toll-like receptors in vitro. Sci Rep. 2016;6:18910.","journal-title":"Sci Rep."},{"key":"2621_CR21","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1186\/s13075-015-0877-x","volume":"17","author":"A Alquraini","year":"2015","unstructured":"Alquraini A, Garguilo S, D\u2019Souza G, Zhang LX, Schmidt TA, Jay GD, et al. The interaction of lubricin\/proteoglycan 4 (PRG4) with Toll-like receptors 2 and 4: an anti-inflammatory role of PRG4 in synovial fluid. Arthritis Res Ther. 2015;17:353.","journal-title":"Arthritis Res Ther."},{"issue":"1","key":"2621_CR22","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13075-017-1301-5","volume":"19","author":"A Alquraini","year":"2017","unstructured":"Alquraini A, Jamal M, Zhang L, Schmidt T, Jay GD, Elsaid KA. The autocrine role of proteoglycan-4 (PRG4) in modulating osteoarthritic synoviocyte proliferation and expression of matrix degrading enzymes. Arthritis Res Ther. 2017;19(1):89.","journal-title":"Arthritis Res Ther."},{"key":"2621_CR23","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13075-020-02207-x","volume":"22","author":"M Qadri","year":"2020","unstructured":"Qadri M, Jay GD, Zhang LX, Richendrfer H, Schmidt TA, Elsaid KA. Proteoglycan-4 regulates fibroblast to myofibroblast transition and expression of fibrotic genes in the synovium. Arthritis Res Ther. 2020;22:113.","journal-title":"Arthritis Res Ther."},{"issue":"3","key":"2621_CR24","doi-asserted-by":"publisher","first-page":"C432","DOI":"10.1152\/ajpcell.00041.2018","volume":"315","author":"MM Qadri","year":"2018","unstructured":"Qadri MM, Jay GD, Ostrom RS, Zhang LX, Elsaid KA. cAMP attenuates TGF-\u03b2\u2019s profibrotic responses in osteoarthritic synoviocytes: involvement of hyaluronan and PRG4. Am J Physiol Cell Physiol. 2018;315(3):C432\u201343.","journal-title":"Am J Physiol Cell Physiol."},{"issue":"3","key":"2621_CR25","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1172\/JCI200522263","volume":"115","author":"DK Rhee","year":"2005","unstructured":"Rhee DK, Marcelino J, Baker M, Gong Y, Smits P, Lefebvre V, et al. The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. J Clin Invest. 2005;115(3):622\u201331.","journal-title":"J Clin Invest."},{"issue":"11","key":"2621_CR26","doi-asserted-by":"publisher","first-page":"3070","DOI":"10.1002\/art.39276","volume":"67","author":"A Hill","year":"2015","unstructured":"Hill A, Waller KA, Cui Y, Allen JM, Smits P, Zhang LX, et al. Lubricin restoration in a mouse model of congenital deficiency. Arthritis Rheumatol. 2015;67(11):3070\u201381.","journal-title":"Arthritis Rheumatol."},{"issue":"8","key":"2621_CR27","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1002\/art.27550","volume":"62","author":"GD Jay","year":"2010","unstructured":"Jay GD, Fleming BC, Watkins BA, McHugh KA, Anderson SC, Zhang LX, et al. Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transection. Arthritis Rheum. 2010;62(8):2382\u201391.","journal-title":"Arthritis Rheum."},{"issue":"7","key":"2621_CR28","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1177\/0363546516686965","volume":"45","author":"KA Waller","year":"2017","unstructured":"Waller KA, Chin KE, Jay GD, Zhang LX, Teeple E, McAllister S, et al. Intra-articular recombinant human proteoglycan-4 mitigates cartilage damage after destabilization of the medial meniscus in the Yucatan minipig. Am J Sports Med. 2017;45(7):1512\u201321.","journal-title":"Am J Sports Med."},{"issue":"1","key":"2621_CR29","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s13075-018-1693-x","volume":"20","author":"M Qadri","year":"2018","unstructured":"Qadri M, Jay GD, Zhang LX, Wong W, Reginato AM, Sun C, et al. Recombinant human proteoglycan-4 reduces phagocytosis of urate crystals and downstream nuclear factor kappa B and inflammasome activation and production of cytokines and chemokines in human and murine macrophages. Arthritis Res Ther. 2018;20(1):192.","journal-title":"Arthritis Res Ther."},{"issue":"3","key":"2621_CR30","doi-asserted-by":"publisher","first-page":"501","DOI":"10.3899\/jrheum.130541","volume":"41","author":"A Guermazi","year":"2014","unstructured":"Guermazi A, Hayashi D, Roemer FW, Zhu Y, Niu J, Crema MD, et al. Synovitis in knee osteoarthritis assessed by contrast-enhanced magnetic resonance imaging (MRI) is associated with radiographic tibiofemoral osteoarthritis and MRI-detected widespread cartilage damage: the MOST study. J Rheumatol. 2014;41(3):501\u20138.","journal-title":"J Rheumatol."},{"issue":"12","key":"2621_CR31","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1016\/j.joca.2012.08.027","volume":"20","author":"BJ de Lange-Brokaar","year":"2012","unstructured":"de Lange-Brokaar BJ, Ioan-Facsinay A, van Osch GJ, Zuurmond A-M, Schoones J, Toes REM, et al. Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage. 2012;20(12):1484\u201399.","journal-title":"Osteoarthritis Cartilage."},{"key":"2621_CR32","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41413-019-0047-x","volume":"7","author":"KM Usher","year":"2019","unstructured":"Usher KM, Zhu S, Mavropalias G, Carrino JA, Zhao J, Xu J. Pathological mechanisms and therapeutic outlooks for arthrofibrosis. Bone Res. 2019;7:9.","journal-title":"Bone Res."},{"issue":"9","key":"2621_CR33","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.imbio.2014.05.002","volume":"219","author":"DY Vogel","year":"2014","unstructured":"Vogel DY, Glim JE, Stavenuiter AW, Breuer M, Heijnen P, Amor S, et al. Human macrophage polarization in vitro: maturation and activation methods compared. Immunobiology. 2014;219(9):695\u2013703.","journal-title":"Immunobiology."},{"issue":"2","key":"2621_CR34","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1002\/JLB.3RU1018-378RR","volume":"106","author":"LX Wang","year":"2019","unstructured":"Wang LX, Zhang SX, Wu HJ, Rong XL, Guo J. M2b macrophage polarization and its roles in diseases. J Leukoc Biol. 2019;106(2):345\u201358.","journal-title":"J Leukoc Biol."},{"issue":"5","key":"2621_CR35","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1189\/jlb.0411203","volume":"90","author":"V Briken","year":"2011","unstructured":"Briken V, Mosser DM. Editorial: switching on arginase in M2 macrophages. J Leukoc Biol. 2011;90(5):839\u201341.","journal-title":"J Leukoc Biol."},{"issue":"2","key":"2621_CR36","doi-asserted-by":"publisher","first-page":"758","DOI":"10.4049\/jimmunol.1700713","volume":"200","author":"M Qadri","year":"2018","unstructured":"Qadri M, Almadani S, Jay GD, Elsaid KA. Role of CD44 in regulating TLR2 activation of human macrophages and downstream expression of proinflammatory cytokines. J Immunol. 2018;200(2):758\u201367.","journal-title":"J Immunol."},{"key":"2621_CR37","doi-asserted-by":"crossref","unstructured":"Misharin AV, Cuda CM, Saber R, Turner JD, Gierut AK, Haines GK, et al. Non-classical Ly6C-monocytes drive the development of inflammatory arthritis in mice. Cell Rep. 2014;9(2):591-604.","DOI":"10.1016\/j.celrep.2014.09.032"},{"key":"2621_CR38","first-page":"14.1","volume":"14","author":"X Zhang","year":"2008","unstructured":"Zhang X, Goncalves R, Mosser D. The isolation and characterization of murine macrophages. Curr. Protoc. Immunol. 2008;14:14.1.","journal-title":"Curr. Protoc. Immunol."},{"key":"2621_CR39","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402\u20138.","journal-title":"Methods."},{"key":"2621_CR40","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.exer.2014.06.015","volume":"127C","author":"ML Samson","year":"2014","unstructured":"Samson ML, Morrison S, Masala N, Sullivan BD, Sullivan DA, Sheardown H, et al. Characterization of full-length recombinant human proteoglycan 4 as an ocular surface boundary lubricant. Exp Eye Res. 2014;127C:14\u20139.","journal-title":"Exp Eye Res."},{"key":"2621_CR41","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s13075-017-1447-1","volume":"19","author":"L Quero","year":"2017","unstructured":"Quero L, Hanser E, Manigold T, Tiaden AN, Kyburz D. TLR2 stimulation impairs anti-inflammatory activity of M2-like macrophages, generating a chimeric M1\/M2 phenotype. Arthritis Res. Ther. 2017;19:245.","journal-title":"Arthritis Res. Ther."},{"issue":"5","key":"2621_CR42","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/cmi.2014.28","volume":"11","author":"JY Li","year":"2014","unstructured":"Li JY, Liu Y, Gao XX, Gao X, Cai H. TLR2 and TLR4 signaling pathways are required for recombinant Brucella abortus BCSP31-induced cytokine production, functional upregulation of mouse macrophages, and the Th1 immune response in vivo and in vitro. Cell Mol Immunol. 2014;11(5):477\u201394.","journal-title":"Cell Mol Immunol."},{"key":"2621_CR43","doi-asserted-by":"crossref","unstructured":"Lech M, Anders HJ. Macrophages and fibrosis: how resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair. Biochem Biophys Acta. 2013;1832(7):989\u20139.","DOI":"10.1016\/j.bbadis.2012.12.001"},{"issue":"2","key":"2621_CR44","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2017-000527","volume":"3","author":"M Kurowska-Stolarska","year":"2017","unstructured":"Kurowska-Stolarska M, Alivernini S. Synovial tissue macrophages: friend or foe? RMD Open. 2017;3(2):e000527.","journal-title":"RMD Open."},{"key":"2621_CR45","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/978-1-60327-360-2_13","volume":"605","author":"N van Roojien","year":"2010","unstructured":"van Roojien N, Hendrikx E. Liposomes for specific depletion of macrophages from organs and tissues. Methods Mol Biol. 2010;605:189\u2013203.","journal-title":"Methods Mol Biol."},{"key":"2621_CR46","doi-asserted-by":"crossref","unstructured":"Blom AB, van lent PL, Libregts S, Holthuysen AE, van der Kraan PM, van Roojien N, et al. Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3. Arthritis Rheum. 2007;56(1):147-157.","DOI":"10.1002\/art.22337"},{"key":"2621_CR47","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/s41598-018-36909-9","volume":"9","author":"AR Sun","year":"2019","unstructured":"Sun AR, Wu X, Liu B, Chen Y, Armitage CW, Kollipara A, et al. Pro-resolving lipid mediator ameliorates obesity induced osteoarthritis by regulating synovial macrophage polarization. Sci Rep. 2019;9:426.","journal-title":"Sci Rep."},{"issue":"4","key":"2621_CR48","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1002\/jor.23471","volume":"35","author":"CR Scanzello","year":"2017","unstructured":"Scanzello CR. Chemokines and inflammation in osteoarthritis: insights from patients and animal models. J Orthop Res. 2017;35(4):735\u20139.","journal-title":"J Orthop Res."},{"key":"2621_CR49","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s13075-021-02457-3","volume":"23","author":"X Zhu","year":"2021","unstructured":"Zhu X, Lee CW, Xu H, Wang Y-F, Yung PS, Jiang Y, et al. Phenotypic alteration of macrophages during osteoarthritis: s systematic review. Arthritis Res Ther. 2021;23:110.","journal-title":"Arthritis Res Ther."},{"issue":"2","key":"2621_CR50","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1002\/art.40696","volume":"71","author":"W Wang","year":"2019","unstructured":"Wang W, Lin X, Xu H, Sun W, Bouta EM, Zuscik MJ, et al. Attenuated joint tissue damage associated with improved synovial lymphatic function following treatment with bortezomib in a mouse model of experimental posttraumatic osteoarthritis. Arthritis Rheumatol. 2019;71(2):244\u201357.","journal-title":"Arthritis Rheumatol."},{"issue":"1","key":"2621_CR51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0206217","volume":"13","author":"N Sambamurthy","year":"2018","unstructured":"Sambamurthy N, Zhou C, Nguyen V, Smalley R, Hankenson KD, Dodge GR, et al. Deficiency of the pattern-recognition receptor CD14 protects against joint pathology and functional decline in a murine model of osteoarthritis. PLoS One. 2018;13(1):e0206217.","journal-title":"PLoS One."}],"updated-by":[{"DOI":"10.1186\/s13075-021-02640-6","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000}}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-021-02621-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13075-021-02621-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-021-02621-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T13:06:07Z","timestamp":1635512767000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-021-02621-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,14]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2621"],"URL":"https:\/\/doi.org\/10.1186\/s13075-021-02621-9","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,14]]},"assertion":[{"value":"6 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2021","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s13075-021-02640-6","URL":"https:\/\/doi.org\/10.1186\/s13075-021-02640-6","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Harvest of joint capsular tissues from mice, intra-articular administration of Pam3CSK4, liposomal clodronate and PBS, and histological evaluations of mice joints and harvest of murine bone marrows were approved by the IACUC committee at Chapman University. All experiments were performed in accordance with the established guidelines and regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MQ, LZ, and JT have nothing to disclose.GJ authored patents on rhPRG4 and holds equity in Lubris LLC, MA, USA.ATS authored patents on rhPRG4, is a paid consultant for Lubris LLC, MA, USA, and holds equity in Lubris LLC, MA, USA.KE authored patents on rhPRG4.The authors have no non-financial competing interests related to this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"241"}}