Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models
Identifieur interne : 000615 ( 2020/Analysis ); précédent : 000614; suivant : 000616Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models
Auteurs : Yuta Fujii ; Hiroaki Inoue ; Yuji Arai ; Seiji Shimomura ; Shuji Nakagawa ; Tsunao Kishida ; Shinji Tsuchida ; Yoichiro Kamada ; Kenta Kaihara ; Toshiharu Shirai ; Ryu Terauchi ; Shogo Toyama ; Kazuya Ikoma ; Osam Mazda ; Yasuo MikamiSource :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2019.
Abstract
Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction.
Url:
DOI: 10.3390/ijms20205100
PubMed: 31618828
PubMed Central: 6834114
Affiliations:
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(K.I.)</nlm:aff></affiliation></author><author><name sortKey="Inoue, Hiroaki" sort="Inoue, Hiroaki" uniqKey="Inoue H" first="Hiroaki" last="Inoue">Hiroaki Inoue</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Arai, Yuji" sort="Arai, Yuji" uniqKey="Arai Y" first="Yuji" last="Arai">Yuji Arai</name><affiliation><nlm:aff id="af2-ijms-20-05100">Department of Sports and Para-Sports Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>shushi@koto.kpu-m.ac.jp</email></nlm:aff></affiliation></author><author><name sortKey="Shimomura, Seiji" sort="Shimomura, Seiji" uniqKey="Shimomura S" first="Seiji" last="Shimomura">Seiji Shimomura</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Nakagawa, Shuji" sort="Nakagawa, Shuji" uniqKey="Nakagawa S" first="Shuji" last="Nakagawa">Shuji Nakagawa</name><affiliation><nlm:aff id="af2-ijms-20-05100">Department of Sports and Para-Sports Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>shushi@koto.kpu-m.ac.jp</email></nlm:aff></affiliation></author><author><name sortKey="Kishida, Tsunao" sort="Kishida, Tsunao" uniqKey="Kishida T" first="Tsunao" last="Kishida">Tsunao Kishida</name><affiliation><nlm:aff id="af3-ijms-20-05100">Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>tsunao@koto.kpu-m.ac.jp</email> (T.K.);<email>mazda@koto.kpu-m.ac.jp</email> (O.M.)</nlm:aff></affiliation></author><author><name sortKey="Tsuchida, Shinji" sort="Tsuchida, Shinji" uniqKey="Tsuchida S" first="Shinji" last="Tsuchida">Shinji Tsuchida</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Kamada, Yoichiro" sort="Kamada, Yoichiro" uniqKey="Kamada Y" first="Yoichiro" last="Kamada">Yoichiro Kamada</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Kaihara, Kenta" sort="Kaihara, Kenta" uniqKey="Kaihara K" first="Kenta" last="Kaihara">Kenta Kaihara</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Shirai, Toshiharu" sort="Shirai, Toshiharu" uniqKey="Shirai T" first="Toshiharu" last="Shirai">Toshiharu Shirai</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Terauchi, Ryu" sort="Terauchi, Ryu" uniqKey="Terauchi R" first="Ryu" last="Terauchi">Ryu Terauchi</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> 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(S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Mazda, Osam" sort="Mazda, Osam" uniqKey="Mazda O" first="Osam" last="Mazda">Osam Mazda</name><affiliation><nlm:aff id="af3-ijms-20-05100">Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>tsunao@koto.kpu-m.ac.jp</email> (T.K.);<email>mazda@koto.kpu-m.ac.jp</email> (O.M.)</nlm:aff></affiliation></author><author><name sortKey="Mikami, Yasuo" sort="Mikami, Yasuo" uniqKey="Mikami Y" first="Yasuo" last="Mikami">Yasuo Mikami</name><affiliation><nlm:aff id="af4-ijms-20-05100">Department of Rehabilitation Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>mikami@koto.kpu-m.ac.jp</email></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno 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(T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Inoue, Hiroaki" sort="Inoue, Hiroaki" uniqKey="Inoue H" first="Hiroaki" last="Inoue">Hiroaki Inoue</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Arai, Yuji" sort="Arai, Yuji" uniqKey="Arai Y" first="Yuji" last="Arai">Yuji Arai</name><affiliation><nlm:aff id="af2-ijms-20-05100">Department of Sports and Para-Sports Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>shushi@koto.kpu-m.ac.jp</email></nlm:aff></affiliation></author><author><name sortKey="Shimomura, Seiji" sort="Shimomura, Seiji" uniqKey="Shimomura S" first="Seiji" last="Shimomura">Seiji Shimomura</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Nakagawa, Shuji" sort="Nakagawa, Shuji" uniqKey="Nakagawa S" first="Shuji" last="Nakagawa">Shuji Nakagawa</name><affiliation><nlm:aff id="af2-ijms-20-05100">Department of Sports and Para-Sports Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>shushi@koto.kpu-m.ac.jp</email></nlm:aff></affiliation></author><author><name sortKey="Kishida, Tsunao" sort="Kishida, Tsunao" uniqKey="Kishida T" first="Tsunao" last="Kishida">Tsunao Kishida</name><affiliation><nlm:aff id="af3-ijms-20-05100">Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>tsunao@koto.kpu-m.ac.jp</email> (T.K.);<email>mazda@koto.kpu-m.ac.jp</email> (O.M.)</nlm:aff></affiliation></author><author><name sortKey="Tsuchida, Shinji" sort="Tsuchida, Shinji" uniqKey="Tsuchida S" first="Shinji" last="Tsuchida">Shinji Tsuchida</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Kamada, Yoichiro" sort="Kamada, Yoichiro" uniqKey="Kamada Y" first="Yoichiro" last="Kamada">Yoichiro Kamada</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Kaihara, Kenta" sort="Kaihara, Kenta" uniqKey="Kaihara K" first="Kenta" last="Kaihara">Kenta Kaihara</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Shirai, Toshiharu" sort="Shirai, Toshiharu" uniqKey="Shirai T" first="Toshiharu" last="Shirai">Toshiharu Shirai</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Terauchi, Ryu" sort="Terauchi, Ryu" uniqKey="Terauchi R" first="Ryu" last="Terauchi">Ryu Terauchi</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Toyama, Shogo" sort="Toyama, Shogo" uniqKey="Toyama S" first="Shogo" last="Toyama">Shogo Toyama</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Ikoma, Kazuya" sort="Ikoma, Kazuya" uniqKey="Ikoma K" first="Kazuya" last="Ikoma">Kazuya Ikoma</name><affiliation><nlm:aff id="af1-ijms-20-05100">Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>y-fujii@koto.kpu-m.ac.jp</email> (Y.F.);<email>hinoue@koto.kpu-m.ac.jp</email> (H.I.);<email>s-shimo@koto.kpu-m.ac.jp</email> (S.S.);<email>tuchi-kf@koto.kpu-m.ac.jp</email> (S.T.);<email>kamada-y@koto.kpu-m.ac.jp</email> (Y.K.);<email>kaihara5@koto.kpu-m.ac.jp</email> (K.K.);<email>shirai.t77@gmail.com</email> (T.S.);<email>ryutel@mbox.kyoto-inet.or.jp</email> (R.T.);<email>shogot@koto.kpu-m.ac.jp</email> (S.T.);<email>kazuya@koto.kpu-m.ac.jp</email> (K.I.)</nlm:aff></affiliation></author><author><name sortKey="Mazda, Osam" sort="Mazda, Osam" uniqKey="Mazda O" first="Osam" last="Mazda">Osam Mazda</name><affiliation><nlm:aff id="af3-ijms-20-05100">Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>tsunao@koto.kpu-m.ac.jp</email> (T.K.);<email>mazda@koto.kpu-m.ac.jp</email> (O.M.)</nlm:aff></affiliation></author><author><name sortKey="Mikami, Yasuo" sort="Mikami, Yasuo" uniqKey="Mikami Y" first="Yasuo" last="Mikami">Yasuo Mikami</name><affiliation><nlm:aff id="af4-ijms-20-05100">Department of Rehabilitation Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;<email>mikami@koto.kpu-m.ac.jp</email></nlm:aff></affiliation></author></analytic><series><title level="j">International Journal of Molecular Sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Nanki, T" uniqKey="Nanki T">T. Nanki</name></author><author><name sortKey="Hayashida, K" uniqKey="Hayashida K">K. Hayashida</name></author><author><name sortKey="El Gabalawy, H S" uniqKey="El Gabalawy H">H.S. El-Gabalawy</name></author><author><name sortKey="Suson, S" uniqKey="Suson S">S. Suson</name></author><author><name sortKey="Shi, K" uniqKey="Shi K">K. Shi</name></author><author><name sortKey="Girschick, H J" uniqKey="Girschick H">H.J. 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