Xuhui Liu1, Sunil Joshi2, Bharat Ravishankar1, Dominique Laron3, Hubert T Kim1, Brian T Feeley1. 1. San Francisco Veterans Affairs Medical Center, Department of Veterans Affairs, San Francisco, USA ; Department of Orthopaedic Surgery, University of California, San Francisco, USA. 2. San Francisco Veterans Affairs Medical Center, Department of Veterans Affairs, San Francisco, USA. 3. Department of Orthopaedic Surgery, University of California, San Francisco, USA.
Abstract
BACKGROUND: reduced mass (atrophy) and increased fat content (fatty infiltration) of rotator cuff muscles are common complications of large or massive rotator cuff (RC) tears, and are believed to be irreversible even after tendon repairs. Clinically, both muscle atrophy and fatty infiltration are important factors contributing to poor functional outcomes after tendon repairs. The molecular mechanism of RC muscle atrophy and FI remains undefined. In this study, we investigated the role of bone morphogenetic proteins (BMP) signaling in RC muscle atrophy and fatty infiltration using a rat model. METHODS: unilateral massive RC tears was induced in adult rats. RC muscles were harvested at 2 and 6 weeks after injury for BMP signaling analysis. In a separate experiment, BMP inhibitor (LDN-193189) was injected to rats through daily intraperitoneal injection. RC muscles from rats in the treated and control groups were harvested at 6 weeks after injury for biochemistry and histology analysis. RESULTS: we found significantly increased BMP-14 and BMP-7 expression in rotator cuff muscles after RCT. Inhibiting BMP signaling resulted in increased muscle atrophy and reduced fatty infiltration in rotator cuff muscle after RC tears. CONCLUSION: this result suggests that BMP signaling inhibits RC muscle atrophy but promotes fatty infiltration.
BACKGROUND: reduced mass (atrophy) and increased fat content (fatty infiltration) of rotator cuff muscles are common complications of large or massive rotator cuff (RC) tears, and are believed to be irreversible even after tendon repairs. Clinically, both muscle atrophy and fatty infiltration are important factors contributing to poor functional outcomes after tendon repairs. The molecular mechanism of RC muscle atrophy and FI remains undefined. In this study, we investigated the role of bone morphogenetic proteins (BMP) signaling in RC muscle atrophy and fatty infiltration using a rat model. METHODS: unilateral massive RC tears was induced in adult rats. RC muscles were harvested at 2 and 6 weeks after injury for BMP signaling analysis. In a separate experiment, BMP inhibitor (LDN-193189) was injected to rats through daily intraperitoneal injection. RC muscles from rats in the treated and control groups were harvested at 6 weeks after injury for biochemistry and histology analysis. RESULTS: we found significantly increased BMP-14 and BMP-7 expression in rotator cuff muscles after RCT. Inhibiting BMP signaling resulted in increased muscle atrophy and reduced fatty infiltration in rotator cuff muscle after RC tears. CONCLUSION: this result suggests that BMP signaling inhibits RC muscle atrophy but promotes fatty infiltration.
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