Concomitant Treatment with Etanercept and Tacrolimus Synergistically Attenuates Arthritis Progression via Inhibition of Matrix Metalloproteinase-3 Production and Osteoclastogenesis in Human TNF-<i>α</i> Transgenic Mice

<div>Etanercept and tacrolimus decrease the population of CD11b<sup>high</sup> peripheral osteoclast precursors in hTNF-Tg mice. Etanercept (ETN; 4 mg/kg) was administered subcutaneously twice a week for 4 weeks, and tacrolimus (TAC; 3 mg/kg) was administered orally once daily for 4 weeks. (a) Percentages of ZombieNIR-negative CD11b<sup>high</sup> cells in splenic cells derived from individual mice are shown. 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602Z"></path></g><g transform="matrix(.013,0,0,-0.013,51.892,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,58.132,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"></path></g></svg> compared with the vehicle group (Dunnet’s multiple comparison test). <svg height="15.61pt" id="M59" style="vertical-align:-3.4295pt" version="1.1" viewbox="-0.0498162 -12.1805 49.4086 15.61" width="49.4086pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M263 363V584C343 572 363 521 380 464L408 470C399 526 392 562 387 596C376 598 367 601 353 604C328 612 296 617 263 617V693H228V615C122 603 67 532 67 453C67 376 123 329 193 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the tacrolimus-treated group (Student’s <span class="nowrap"><svg height="8.02022pt" id="M60" style="vertical-align:-0.2063999pt" version="1.1" viewbox="-0.0498162 -7.81382 4.54925 8.02022" width="4.54925pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M324 430H196L233 583L223 592L145 529L120 430H54L29 396L31 388H111L56 126C33 15 54 -12 77 -12C137 -12 214 57 250 95L233 119C208 92 155 59 138 59C126 59 120 70 131 125L186 390L298 394L324 430Z"></path></g></svg>-</span>test). (b) Representative plots of each drug treatment group are shown. Data are representative of two independent experiments.</div>

Mediators of Inflammation

fig4

Figure 4

Figure 4: Concomitant Treatment with Etanercept and Tacrolimus Synergistically Attenuates Arthritis Progression via Inhibition of Matrix Metalloproteinase-3 Production and Osteoclastogenesis in Human TNF-<i>α</i> Transgenic Mice 

Figure 4 | Concomitant Treatment with Etanercept and Tacrolimus Synergistically Attenuates Arthritis Progression via Inhibition of Matrix Metalloproteinase-3 Production and Osteoclastogenesis in Human TNF-α Transgenic Mice 