Periostin Promotes Fibroblast Migration and Inhibits Muscle Repair After Skeletal Muscle Injury

Masamitsu Hara, Kazuya Yokota, Takeyuki Saito, Kazu Kobayakawa, Ken Kijima, Shingo Yoshizaki, Ken Okazaki, Shigeo Yoshida, Yoshihiro Matsumoto, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada

Research output: Contribution to journalArticle

Abstract

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 findings may provide a potential therapeutic strategy to enhance muscle repair and functional recovery after SMI.

Original languageEnglish
Pages (from-to)e108
JournalThe Journal of bone and joint surgery. American volume
Volume100
Issue number16
DOIs
Publication statusPublished - Aug 15 2018

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Skeletal Muscle
Fibroblasts
Muscles
Wounds and Injuries
Fibrosis
Muscle Development
Lacerations
Muscle Strength
Neutralizing Antibodies
Knockout Mice
Cicatrix
Regeneration
Immunoglobulin G
Immunohistochemistry
Confidence Intervals
Gene Expression
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Orthopedics and Sports Medicine

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Periostin Promotes Fibroblast Migration and Inhibits Muscle Repair After Skeletal Muscle Injury. / Hara, Masamitsu; Yokota, Kazuya; Saito, Takeyuki; Kobayakawa, Kazu; Kijima, Ken; Yoshizaki, Shingo; Okazaki, Ken; Yoshida, Shigeo; Matsumoto, Yoshihiro; Harimaya, Katsumi; Nakashima, Yasuharu; Okada, Seiji.

In: The Journal of bone and joint surgery. American volume, Vol. 100, No. 16, 15.08.2018, p. e108.

Research output: Contribution to journalArticle

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abstract = "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 findings may provide a potential therapeutic strategy to enhance muscle repair and functional recovery after SMI.",
author = "Masamitsu Hara and Kazuya Yokota and Takeyuki Saito and Kazu Kobayakawa and Ken Kijima and Shingo Yoshizaki and Ken Okazaki and Shigeo Yoshida and Yoshihiro Matsumoto and Katsumi Harimaya and Yasuharu Nakashima and Seiji Okada",
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T1 - Periostin Promotes Fibroblast Migration and Inhibits Muscle Repair After Skeletal Muscle Injury

AU - Hara, Masamitsu

AU - Yokota, Kazuya

AU - Saito, Takeyuki

AU - Kobayakawa, Kazu

AU - Kijima, Ken

AU - Yoshizaki, Shingo

AU - Okazaki, Ken

AU - Yoshida, Shigeo

AU - Matsumoto, Yoshihiro

AU - Harimaya, Katsumi

AU - Nakashima, Yasuharu

AU - Okada, Seiji

PY - 2018/8/15

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