Inflammatory processes in muscle injury and repair

2005 ◽  
Vol 288 (2) ◽  
pp. R345-R353 ◽  
Author(s):  
James G. Tidball
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Cell Invasion ◽  
Muscle Injury ◽  
Inflammatory Cell ◽  
Inflammatory Cells ◽  
Muscle Repair ◽  
Injury And Repair

Modified muscle use or injury can produce a stereotypic inflammatory response in which neutrophils rapidly invade, followed by macrophages. This inflammatory response coincides with muscle repair, regeneration, and growth, which involve activation and proliferation of satellite cells, followed by their terminal differentiation. Recent investigations have begun to explore the relationship between inflammatory cell functions and skeletal muscle injury and repair by using genetically modified animal models, antibody depletions of specific inflammatory cell populations, or expression profiling of inflamed muscle after injury. These studies have contributed to a complex picture in which inflammatory cells promote both injury and repair, through the combined actions of free radicals, growth factors, and chemokines. In this review, recent discoveries concerning the interactions between skeletal muscle and inflammatory cells are presented. New findings clearly show a role for neutrophils in promoting muscle damage soon after muscle injury or modified use. No direct evidence is yet available to show that neutrophils play a beneficial role in muscle repair or regeneration. Macrophages have also been shown capable of promoting muscle damage in vivo and in vitro through the release of free radicals, although other findings indicate that they may also play a role in muscle repair and regeneration through growth factors and cytokine-mediated signaling. However, this role for macrophages in muscle regeneration is still not definitive; other cells present in muscle can also produce the potentially regenerative factors, and it remains to be proven whether macrophage-derived factors are essential for muscle repair or regeneration in vivo. New evidence also shows that muscle cells can release positive and negative regulators of inflammatory cell invasion, and thereby play an active role in modulating the inflammatory process. In particular, muscle-derived nitric oxide can inhibit inflammatory cell invasion of healthy muscle and protect muscle from lysis by inflammatory cells in vivo and in vitro. On the other hand, muscle-derived cytokines can signal for inflammatory cell invasion, at least in vitro. The immediate challenge for advancing our current understanding of the relationships between muscle and inflammatory cells during muscle injury and repair is to place what has been learned in vitro into the complex and dynamic in vivo environment.

The Biological Use of Platelet-Rich Plasma in Skeletal Muscle Injury and Repair

2021 ◽  
pp. 036354652110616
Author(s):  
Jordan Boivin ◽  
Rachael Tolsma ◽  
Peter Awad ◽  
Keith Kenter ◽  
Yong Li
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Regenerative Medicine ◽  
Sports Medicine ◽  
Muscle Injury ◽  
Blood Product ◽  
Platelet Rich Plasma ◽  
Injury And Repair ◽  
Current Report

Platelet-rich plasma (PRP) is a blood product that contains several growth factors and active proteins. PRP is thought to be used autologously to assist in the repair of injured tissues as well as to treat pain at the site of injury. The mechanism behind PRP in regenerative medicine has been well investigated and includes the identification and concentration of released growth factors and exosomes. The benefits of PRP have been highly recommended and are used widely in orthopaedics and sports medicine, including repair of injured skeletal muscle. This current report summarizes some of the more recent studies in the use of PRP as it relates to muscle healing, in both the in vitro and clinical arenas.

Effect of overexpression of pparγ on the healing process of corneal alkali burn in mice

2007 ◽  
Vol 293 (1) ◽  
pp. C75-C86 ◽  
Author(s):  
Shizuya Saika ◽  
Osamu Yamanaka ◽  
Yuka Okada ◽  
Takeshi Miyamoto ◽  
Ai Kitano ◽  
...  
Keyword(s):  
Growth Factors ◽  
Ocular Surface ◽  
Nuclear Translocation ◽  
Healing Process ◽  
Inflammatory Cells ◽  
Peroxisome Proliferator ◽  
Growth Factor Signaling ◽  
Alkali Burn

Wound healing involves both local cells and inflammatory cells. Alkali burn of ocular surface tissue is a serious clinical problem often leading to permanent visual impairment resulting from ulceration, scarring and neovascularization during healing. Behaviors of corneal cells and inflammatory cells are orchestrated by growth factor signaling networks that have not been fully uncovered. Here we showed that adenoviral gene introduction of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits activation of ocular fibroblasts and macrophages in vitro and also induced anti-inflammatory and anti-fibrogenic responses in an alkali-burned mouse cornea. PPARγ overexpression suppressed upregulation of inflammation/scarring-related growth factors and matrix metalloproteinases (MMPs) in macrophages. It also suppressed expression of such growth factors and collagen Iα2 and myofibroblast generation upon exposure to TGFβ1. Exogenous PPARγ did not alter phosphorylation of Smad2, but inhibited its nuclear translocation. PPARγ overexpression enhanced proliferation of corneal epithelial cells, but not of fibroblasts in vitro. Epithelial cell expression of MMP-2/-9 and TGFβ1 and its migration were suppressed by PPARγ overexpression. In vivo experiments showed that PPARγ gene introduction suppressed monocytes/macrophages invasion and suppressed the generation of myofibroblasts, as well as upregulation of cytokines/growth factors and MMPs in a healing cornea. In vivo re-epitheliazation with basement membrane reconstruction in the healing, burned, cornea was accelerated by PPARγ-Ad expression, although PPARγ overexpression was considered to be unfavorable for cell migration. Together, these data suggest that overexpression of PPARγ may represent an effective new strategy for treatment of ocular surface burns.

scholarly journals Defining Akt actions in muscle differentiation

2012 ◽  
Vol 303 (12) ◽  
pp. C1292-C1300 ◽  
Author(s):  
Samantha Gardner ◽  
Magdalena Anguiano ◽  
Peter Rotwein
Keyword(s):  
Growth Factors ◽  
Muscle Development ◽  
Muscle Growth ◽  
Muscle Differentiation ◽  
In Vivo Studies ◽  
Cell Contact ◽  
Muscle Repair ◽  
Complex Signals

Muscle development in childhood and muscle regeneration in adults are highly regulated processes that are necessary for reaching and maintaining optimal muscle mass and strength throughout life. Muscle repair after injury relies on stem cells, termed satellite cells, whose activity is controlled by complex signals mediated by cell-cell contact, by growth factors, and by hormones, which interact with genetic programs controlled by myogenic transcription factors. Insulin-like growth factors (IGFs) play key roles in muscle development and help coordinate muscle repair after injury, primarily by stimulating the phosphatidylinositol 3-kinase-Akt signaling pathway, and both in vitro and in vivo studies have shown that Akt kinase activity is critical for optimal muscle growth and regeneration. Here we find that of the two Akts expressed in muscle, Akt1 is essential for initiation of differentiation in culture and is required for normal myoblast motility, while Akt2 is dispensable. Although Akt2 deficiency did lead to diminished myotube maturation, as assessed by a decline in myofiber area and in fusion index, either Akt1 or Akt2 could restore these processes toward normal. Thus levels of Akt expression rather than distinct actions of individual Akt species are critical for normal myofiber development during the later stages of muscle differentiation.

scholarly journals Endogenous Galectin-3 is Required for Skeletal Muscle Repair

2020 ◽  
Author(s):  
Daniel Giuliano Cerri ◽  
Lilian Cataldi Rodrigues ◽  
Vani Maria Alves ◽  
Juliano Machado ◽  
Víctor Alexandre Félix Bastos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Culture ◽  
Molecular Mechanisms ◽  
Repair Process ◽  
Muscle Repair ◽  
Galectin 3 ◽  
Self Repair ◽  
Myoblast Cell

ABSTRACTSkeletal muscle has the intrinsic ability to self-repair through a multifactorial process, but many aspects of its cellular and molecular mechanisms are not fully understood. There is increasing evidence that some members of the mammalian β-galactoside-binding protein family (galectins) are involved in the muscular repair process (MRP), including galectin-3 (Gal-3). However, there are many questions about the role of this protein on muscle self-repair. Here, we demonstrate that endogenous Gal-3 is required for: i) muscle repair in vivo using a chloride-barium myolesion mouse model, and ii) mouse primary myoblasts myogenic programming. Injured muscle from Gal-3 knockout mice (GAL3KO) showed persistent inflammation associated with compromised muscle repair and the formation of fibrotic tissue on the lesion site. In GAL3KO mice, osteopontin expression remained high even after 7 and 14 days of the myolesion, while MyoD and myogenin had decreased their expression. In GAL3KO mouse primary myoblast cell culture, Pax7 detection seems to sustain even when cells are stimulated to differentiation and MyoD expression is drastically reduced. These findings suggest that the detection and temporal expression levels of these transcriptional factors appear to be altered in Gal-3-deficient myoblast cell culture compared to Wild Type (WT) cells. We observed Gal-3 expression in WT states, both in vivo and in vitro, in sarcoplasm/cytoplasm and myonuclei; as differentiation proceeds, Gal-3 expression is drastically reduced, and its location is confined to the sarcolemma/plasma cell membrane. We also observed a change in the temporal-spatial profile of Gal-3 expression and muscle transcription factors levels during the myolesion. Overall, these results demonstrate that endogenous Gal-3 is required for the skeletal muscle repair process.

scholarly journals Pro-myogenic small molecules revealed by a chemical screen on primary muscle stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sean M. Buchanan ◽  
Feodor D. Price ◽  
Alessandra Castiglioni ◽  
Amanda Wagner Gee ◽  
Joel Schneider ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Small Molecules ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Repair ◽  
Muscle Stem Cells

Abstract Satellite cells are the canonical muscle stem cells that regenerate damaged skeletal muscle. Loss of function of these cells has been linked to reduced muscle repair capacity and compromised muscle health in acute muscle injury and congenital neuromuscular diseases. To identify new pathways that can prevent loss of skeletal muscle function or enhance regenerative potential, we established an imaging-based screen capable of identifying small molecules that promote the expansion of freshly isolated satellite cells. We found several classes of receptor tyrosine kinase (RTK) inhibitors that increased freshly isolated satellite cell numbers in vitro. Further exploration of one of these compounds, the RTK inhibitor CEP-701 (also known as lestaurtinib), revealed potent activity on mouse satellite cells both in vitro and in vivo. This expansion potential was not seen upon exposure of proliferating committed myoblasts or non-myogenic fibroblasts to CEP-701. When delivered subcutaneously to acutely injured animals, CEP-701 increased both the total number of satellite cells and the rate of muscle repair, as revealed by an increased cross-sectional area of regenerating fibers. Moreover, freshly isolated satellite cells expanded ex vivo in the presence of CEP-701 displayed enhanced muscle engraftment potential upon in vivo transplantation. We provide compelling evidence that certain RTKs, and in particular RET, regulate satellite cell expansion during muscle regeneration. This study demonstrates the power of small molecule screens of even rare adult stem cell populations for identifying stem cell-targeting compounds with therapeutic potential.

Tristetraprolin and LPS-inducible CXC chemokine are rapidly induced in presumptive satellite cells in response to skeletal muscle injury

2002 ◽  
Vol 115 (13) ◽  
pp. 2701-2712 ◽  
Author(s):  
Chetana Sachidanandan ◽  
Ramkumar Sambasivan ◽  
Jyotsna Dhawan
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Cell Biology ◽  
Muscle Injury ◽  
Rna Binding ◽  
C2c12 Myoblasts ◽  
Adult Skeletal Muscle ◽  
Cxc Chemokine

Myogenic precursor cells known as satellite cells persist in adult skeletal muscle and are responsible for its ability to regenerate after injury. Quiescent satellite cells are activated by signals emanating from damaged muscle. Here we describe the rapid activation of two genes in response to muscle injury; these transcripts encode LPS-inducible CXC chemokine (LIX), a neutrophil chemoattractant, and Tristetraprolin (TTP), an RNA-binding protein implicated in the regulation of cytokine expression. Using a synchronized cell culture model we show that C2C12 myoblasts arrested in G0 exhibit some molecular attributes of satellite cells in vivo: suppression of MyoD and Myf5 expression during G0 and their reactivation in G1. Synchronization also revealed cell cycle dependent expression of CD34, M-cadherin, HGF and PEA3, genes implicated in satellite cell biology. To identify other genes induced in synchronized C2C12 myoblasts we used differential display PCR and isolated LIX and TTP cDNAs. Both LIX and TTP mRNAs are short-lived, encode molecules implicated in inflammation and are transiently induced during growth activation in vitro. Further, LIX and TTP are rapidly induced in response to muscle damage in vivo. TTP expression precedes that of MyoD and is detected 30 minutes after injury. The spatial distribution of LIX and TTP transcripts in injured muscle suggests expression by satellite cells. Our studies suggest that in addition to generating new cells for repair, activated satellite cells may be a source of signaling molecules involved in tissue remodeling during regeneration.

scholarly journals Treatment of Skeletal Muscle Injury: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
L. Baoge ◽  
E. Van Den Steen ◽  
S. Rimbaut ◽  
N. Philips ◽  
E. Witvrouw ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Functional Recovery ◽  
Sports Medicine ◽  
Healing Process ◽  
Muscle Injuries ◽  
Inflammatory Phase ◽  
Tgf Β1

Skeletal muscle injuries are the most common sports-related injuries and present a challenge in primary care and sports medicine. Most types of muscle injuries would follow three stages: the acute inflammatory and degenerative phase, the repair phase and the remodeling phase. Present conservative treatment includes RICE (rest, ice, compression, elevation), nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy. However, if use improper, NSAIDs may suppress an essential inflammatory phase in the healing of injured skeletal muscle. Furthermore, it remains controversial whether or not they have adverse effects on the healing process or on the tensile strength. However, several growth factors might promote the regeneration of injured skeletal muscle, many novel treatments have involved on enhancing complete functional recovery. Exogenous growth factors have been shown to regulate satellite cell proliferation, differentiation and fusion in myotubes in vivo and in vitro, TGF-β1 antagonists behave as inhibitors of TGF-β1. They prevent collagen deposition and block formation of muscle fibrosis, so that a complete functional recovery can be achieved.

scholarly journals Annexin A1 drives macrophage skewing towards a resolving phenotype to accelerate the regeneration of muscle injury through AMPK activation

2018 ◽  
Author(s):  
Simon McArthur ◽  
Thomas Gobbetti ◽  
Gaëtan Juban ◽  
Thibaut Desgeorges ◽  
Marine Theret ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Muscle Fibres ◽  
Annexin A1 ◽  
Skeletal Muscle Injury ◽  
Cellular Processes ◽  
Reparative Process ◽  
Injury And Repair ◽  
Inflammation Resolution

SummaryUnderstanding the circuits that promote an efficient resolution of inflammation is crucial to deciphering the molecular and cellular processes required to promote tissue repair. Macrophages play a central role in the regulation of inflammation, resolution and repair/regeneration. Using a model of skeletal muscle injury and repair, herein we identify Annexin A1 (AnxA1) as the extracellular trigger of macrophage skewing towards a pro-reparative phenotype. Brought into the injured tissue initially by migrated neutrophils, and then over-expressed in infiltrating macrophages, AnxA1 activates FPR2/ALX receptors and the downstream AMPK signalling cascade leading to macrophage skewing, dampening of inflammation and regeneration of muscle fibres. Mice lacking AnxA1 in all cells or in myeloid cells only display a defect in this reparative process.In vitroexperiments recapitulated these properties, with AMPK null macrophages lacking AnxA1-mediated polarization. Collectively, these data identify the AnxA1/FPR2/AMPK axis as a novel pathway in skeletal muscle injury regeneration.

Magnetic Targeting Improves the Therapeutic Efficacy of Microbubble-Mediated Obstructive Thrombus Sonothrombolysis

2019 ◽  
Vol 119 (11) ◽  
pp. 1752-1766 ◽  
Author(s):  
Xiaoqiang Chen ◽  
Weilan Wu ◽  
Shifei Wang ◽  
Jiayuan Zhong ◽  
Nima Moumin Djama ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Flow Velocity ◽  
Blood Flow Velocity ◽  
Muscle Injury ◽  
Magnetic Targeting ◽  
Skeletal Muscle Injury ◽  
The Us

Background Magnetic targeting may help microbubbles (MBs) reach obstructive thrombi and improve the efficacy of MB-mediated sonothrombolysis, but the role of magnetic targeting in MB-mediated sonothrombolysis remains elusive. Objectives We investigate the feasibility and efficacy of magnetically targeted MB-mediated sonothrombolysis for the treatment of obstructive thrombi. Materials and Methods Red and white thromboembolic models were established in vitro and in vivo. The models were randomly assigned to the control, ultrasound plus control MB (US + C-MB), ultrasound plus magnetic MB (US + M-MB), or US + M-MB + recombinant tissue-type plasminogen activator (r-tPA) groups and treated for 30 minutes. The recanalization rate, average blood flow velocity, hindlimb perfusion, and skeletal muscle injury marker levels were recorded. Results The recanalization rate, average blood flow velocity, and hindlimb perfusion in the red and white thromboembolic models were all significantly higher in the US + M-MB and US + M-MB + r-tPA groups than in the control and US + C-MB groups both in vitro and in vivo. Moreover, the levels of the skeletal muscle injury markers were all significantly lower in the US + M-MB and US + M-MB + r-tPA groups than in the other two groups in vivo for both thromboembolic models. However, the thrombolytic effects of red thrombi performed better than those of white thrombi in the US + M-MB + r-tPA group. Conclusion M-MB-mediated sonothrombolysis improves the efficacy of thrombolysis both in vitro and in vivo, and reduces tissue damage in clogging model; thus, this method may serve as a promising approach for treating thrombus-occlusive diseases.

In vitro Evaluation of Macrophage Adhesion and Proliferation on Alumina

2006 ◽  
Vol 950 ◽  
Author(s):  
Peishan Liu-Snyder ◽  
Thomas J. Webster
Keyword(s):  
Grain Size ◽  
Inflammatory Cell ◽  
Inflammatory Cells ◽  
Bone Cell ◽  
Cell Responses ◽  
Nanophase Materials ◽  
Macrophage Adhesion ◽  
Dental Applications

ABSTRACTExtensive interactions of inflammatory cells (such as macrophages) with biomaterials at the host-implant interface are often blamed for failure of implanted biomedical devices [1]. While previous studies have shown increased in vitro and in vivo bone cell (osteoblast) responses on nanophase ceramics [2], few (if any) studies have been conducted to elucidate inflammatory cell responses on such novel materials. In this study, we reported that macrophage adhesion and proliferation on nanophase (97.7 nm grain size) alumina (Al2O3) was significantly less than conventional (187.4 nm grain size) alumina, respectively, after 4, 12, 24 h. The present study provides evidence of the ability of nanophase alumina to down-regulate macrophage adhesion and proliferation, which is imperative for the future consideration of nanophase materials for orthopedic and dental applications.

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