Scholarlink

Background <p>Muscle passive and active function is dependent on the extracellular matrix (ECM). In diseases characterized by muscle fibrosis, namely Duchenne Muscular Dystrophy (DMD), the ECM contributes to deficits in muscle mechanical function and regeneration. Because fibrosis is often viewed as irreversible in DMD and other muscle diseases, there is great incentive to develop anti-fibrotic therapies to prevent or reverse fibrosis.</p> Methods <p>In this study we tested the effectiveness of intramuscular injections of non-specific <i>Clostridium histolyticum collagenase</i> (CCH) on reducing ECM contents and rescuing muscle mechanical function in D2.<i>mdx</i> mice, models of DMD. We performed unilateral injections of collagenase into the tibialis anterior and gastrocnemius in WT and D2.<i>mdx</i> mice. We measured in vivo plantarflexion strength, ex vivo muscle mechanical function, immunohistochemistry, and total and cross-linked collagen content.</p> Results <p>We found that crude CCH was effective at digesting the muscle ECM but did not provide a therapeutic benefit evidenced by induction of muscle weakness and bleeding within 24&#xa0;h after CCH injections, and a thickened basal lamina after 7 days.</p> Conclusions <p>We conclude that future studies testing collagenase as an anti-fibrotic should use a collagenase specific to fibrillar collagens and a paired physical therapy protocol to better preserve muscle function while reducing fibrosis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Targeting muscle fibrosis using non-specific collagenase injections destabilizes the basal lamina and induces matrix remodeling

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月19日

查看全文
  • Ross P. Wohlgemuth,
  • Sathvik Sriram,
  • Sarah E. Brashear,
  • Kyle E. Henricson,
  • Jason J. Howard,
  • Lucas R. Smith

摘要

Background

Muscle passive and active function is dependent on the extracellular matrix (ECM). In diseases characterized by muscle fibrosis, namely Duchenne Muscular Dystrophy (DMD), the ECM contributes to deficits in muscle mechanical function and regeneration. Because fibrosis is often viewed as irreversible in DMD and other muscle diseases, there is great incentive to develop anti-fibrotic therapies to prevent or reverse fibrosis.

Methods

In this study we tested the effectiveness of intramuscular injections of non-specific Clostridium histolyticum collagenase (CCH) on reducing ECM contents and rescuing muscle mechanical function in D2.mdx mice, models of DMD. We performed unilateral injections of collagenase into the tibialis anterior and gastrocnemius in WT and D2.mdx mice. We measured in vivo plantarflexion strength, ex vivo muscle mechanical function, immunohistochemistry, and total and cross-linked collagen content.

Results

We found that crude CCH was effective at digesting the muscle ECM but did not provide a therapeutic benefit evidenced by induction of muscle weakness and bleeding within 24 h after CCH injections, and a thickened basal lamina after 7 days.

Conclusions

We conclude that future studies testing collagenase as an anti-fibrotic should use a collagenase specific to fibrillar collagens and a paired physical therapy protocol to better preserve muscle function while reducing fibrosis.