オカザキ ケン   KEN OKAZAKI
  岡崎 賢
   所属   医学部 医学科(東京女子医科大学病院)
   職種   教授・基幹分野長
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Periostin Promotes Fibroblast Migration and Inhibits Muscle Repair After Skeletal Muscle Injury.
掲載誌名 正式名:The Journal of bone and joint surgery. American volume
略  称:J Bone Joint Surg Am
ISSNコード:15351386/00219355
掲載区分国外
巻・号・頁 100(16),pp.e108
著者・共著者 Hara Masamitsu, Yokota Kazuya, Saito Takeyuki, Kobayakawa Kazu, Kijima Ken, Yoshizaki Shingo, Okazaki Ken, Yoshida Shigeo, Matsumoto Yoshihiro, Harimaya Katsumi, Nakashima Yasuharu, Okada Seiji
発行年月 2018/08
概要 BACKGROUND:Skeletal muscle injury (SMI) can cause physical disability due to insufficient recovery of the muscle. The development of muscle fibrosis after SMI has been widely regarded as a principal cause of this failure to recover. Periostin (Postn) exacerbates tissue fibrosis in various organs. We investigated whether Postn is involved in the pathophysiology after SMI.METHODS:Partial laceration injuries of the gastrocnemius were created in wild-type (WT) and Postn knockout (Postn) mice. We examined the expression of the Postn gene before and after SMI. Regeneration and fibrosis of skeletal muscle were evaluated by histological analyses, and recovery of muscle strength was measured by physiological testing. Immunohistochemistry was used to examine the number and proliferative potential of infiltrating fibroblasts in injured muscle. A trans-well migration assay was used to assess the migration capability of fibroblasts. Control immunoglobulin G (IgG) or Postn-neutralizing antibody (Postn-nAb) was injected into injured muscle at 7 and 14 days after injury (dpi). We evaluated the effects of Postn-nAb on muscle repair after SMI.RESULTS:The expression of Postn was dramatically upregulated after SMI. Compared with WT mice, Postn mice had improved muscle recovery and attenuated fibrosis as well as a significantly reduced number of infiltrating fibroblasts. The proliferative potential of these fibroblasts in WT and Postn mice was comparable at 14 dpi; however, the migration capability of fibroblasts was significantly enhanced in the presence of Postn (mean, 258%; 95% confidence interval, 183% to 334%). Moreover, the administration of Postn-nAb inhibited fibroblast infiltration and promoted muscle repair after SMI.CONCLUSIONS:Postn exacerbates fibrotic scar formation through the promotion of fibroblast migration into injured muscle after SMI. Treatment with Postn-nAb is effective for attenuating fibrosis and improving muscle recovery after SMI.CLINICAL RELEVANCE:Our finding
DOI 10.2106/JBJS.17.01230
PMID 30106825