A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice

Matrix metalloproteinases have been implicated in muscular dystrophy progression and recent studies described the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its implication in dystrophin deficient hearts is still missing. Here, we aimed at investigating MMP-10 implication in severe muscular dystrophic progression and characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We have found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, identifying a new area of investigation that could lead to future therapies for dystrophic muscles.

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Deficiency of MMP-10 Aggravates the Diseased Phenotype of Aged Dystrophic Mice

Life ◽

10.3390/life11121398 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1398

Author(s):

Arantxa Baraibar-Churio ◽

Míriam Bobadilla ◽

Florencio J. D. Machado ◽

Neira Sáinz ◽

Carmen Roncal ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscular Dystrophy ◽

Hind Limb ◽

Survival Rates ◽

Muscle Pathology ◽

Mdx Mice ◽

Chronic Inflammatory Response ◽

Cardiac Muscles ◽

Dystrophic Mice

Matrix metalloproteinases (MMPs) have been implicated in the progression of muscular dystrophy, and recent studies have reported the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its involvement in dystrophin-deficient hearts remains unexplored. Here, we aimed to investigate the involvement of MMP-10 in the progression of severe muscular dystrophy and to characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, thus identifying a new area of research that could lead to future therapies for dystrophic muscles.

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Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models

JRSM Cardiovascular Disease ◽

10.1177/2048004019879581 ◽

2019 ◽

Vol 8 ◽

pp. 204800401987958

Author(s):

HR Spaulding ◽

C Ballmann ◽

JC Quindry ◽

MB Hudson ◽

JT Selsby

Keyword(s):

Skeletal Muscle ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Disease Progression ◽

Gene Mutations ◽

Dystrophin Gene ◽

Mdx Mice ◽

Dystrophin Deficiency ◽

Muscle Wasting Disease ◽

Dystrophin Protein

Background Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. Methods Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. Results Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn± mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. Conclusion Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction.

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Use of Vicryl (Polyglactin 910) Mesh to Limit Epidural Scar Formation after Laminectomy

Neurosurgery ◽

10.1227/00006123-199004000-00014 ◽

1990 ◽

Vol 26 (4) ◽

pp. 649-654 ◽

Cited By ~ 51

Author(s):

Charles E. Nussbaum ◽

Joseph V. McDonald ◽

Raymond B. Baggs

Keyword(s):

Inflammatory Response ◽

Subcutaneous Fat ◽

Inflammatory Cells ◽

Scar Formation ◽

Good Survival ◽

Polyglactin 910 ◽

Chronic Inflammatory Response ◽

Fat Grafts ◽

Free Grafts ◽

Vicryl Mesh

Abstract A variety of substances have been used at laminectomy sites to prevent postoperative epidural scarring. Free grafts of autologous subcutaneous fat are commonly used both clinically and experimentally. The free fat grafts usually survive, but decrease in size by about 50%. Postoperatively, subcutaneous seroma has been observed with the use of fat grafts, as well as recurrent symptoms of neural compression by the graft that required additional operations. When compared to the use of free fat grafts after laminectomy in dogs, Vicryl mesh produced slightly more scarring, but consistently less than that observed in control animals. The Vicryl mesh was resorbed by a minimal chronic inflammatory response over about 45 days. Seven of 11 fat-grafted zones showed signs of necrosis, at times with a greater collection of inflammatory cells than that associated with the Vicryl mesh. Of the 4 fat-grafted zones that showed good survival. 2 had gross evidence of neural compression. No surgical zone treated with Vicryl mesh exhibited evidence of neural compression. In view of these results, the use of Vicryl mesh at laminectomy sites may be a safer method of limiting postoperative epidural scar formation.

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Systemic administration of fractions from Nyctanthes arbor-tristis attenuates chronic inflammatory response in Freund′s-complete-adjuvant-induced arthritis in rats

International Journal of Green Pharmacy ◽

10.4103/0973-8258.140168 ◽

2014 ◽

Vol 8 (3) ◽

pp. 147

Author(s):

Swapnil Goyal ◽

NavinR Sheth ◽

DN Srivastava

Keyword(s):

Inflammatory Response ◽

Systemic Administration ◽

Chronic Inflammatory Response ◽

Adjuvant Induced Arthritis

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9: LYMPHEDEMA IS A FIBROPROLIFERATIVE CONDITION ASSOCIATED WITH A PRO-FIBROTIC CHRONIC INFLAMMATORY RESPONSE

Plastic & Reconstructive Surgery ◽

10.1097/01.prs.0000371745.47053.10 ◽

2010 ◽

Vol 125 (Supplement) ◽

pp. 14

Author(s):

T Avraham ◽

SV Daluvoy ◽

JC Zampell ◽

A Yan ◽

E Kueberuwa

Keyword(s):

Inflammatory Response ◽

Chronic Inflammatory Response

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Aquaporin‐4 deficiency in skeletal muscle and brain of dystrophic mdx mice

The FASEB Journal ◽

10.1096/fj.00-0260com ◽

2001 ◽

Vol 15 (1) ◽

pp. 90-98 ◽

Cited By ~ 134

Author(s):

ANTONIO FRIGERI ◽

GRAZIA PAOLA NICCHIA ◽

BEATRICE NICO ◽

FABIO QUONDAMATTEO ◽

RAINER HERKEN ◽

...

Keyword(s):

Skeletal Muscle ◽

Aquaporin 4 ◽

Mdx Mice

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Early metabolic changes measured by 1H MRS in healthy and dystrophic muscle after injury

Journal of Applied Physiology ◽

10.1152/japplphysiol.00530.2012 ◽

2012 ◽

Vol 113 (5) ◽

pp. 808-816 ◽

Cited By ~ 14

Author(s):

Su Xu ◽

Stephen J. P. Pratt ◽

Espen E. Spangenburg ◽

Richard M. Lovering

Keyword(s):

Skeletal Muscle ◽

Muscle Injury ◽

Tibialis Anterior Muscle ◽

Metabolic Changes ◽

Mdx Mice ◽

Resonance Spectroscopy ◽

Dystrophic Muscle ◽

1H Mrs ◽

Skeletal Muscle Injury

Skeletal muscle injury is often assessed by clinical findings (history, pain, tenderness, strength loss), by imaging, or by invasive techniques. The purpose of this work was to determine if in vivo proton magnetic resonance spectroscopy (1H MRS) could reveal metabolic changes in murine skeletal muscle after contraction-induced injury. We compared findings in the tibialis anterior muscle from both healthy wild-type (WT) muscles (C57BL/10 mice) and dystrophic ( mdx mice) muscles (an animal model for human Duchenne muscular dystrophy) before and after contraction-induced injury. A mild in vivo eccentric injury protocol was used due to the high susceptibility of mdx muscles to injury. As expected, mdx mice sustained a greater loss of force (81%) after injury compared with WT (42%). In the uninjured muscles, choline (Cho) levels were 47% lower in the mdx muscles compared with WT muscles. In mdx mice, taurine levels decreased 17%, and Cho levels increased 25% in injured muscles compared with uninjured mdx muscles. Intramyocellular lipids and total muscle lipid levels increased significantly after injury but only in WT. The increase in lipid was confirmed using a permeable lipophilic fluorescence dye. In summary, loss of torque after injury was associated with alterations in muscle metabolite levels that may contribute to the overall injury response in mdx mice. These results show that it is possible to obtain meaningful in vivo 1H MRS regarding skeletal muscle injury.

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