FAP Beige Adipogenesis in Volumetric Muscle Loss

Abstract Background Volumetric muscle loss (VML) often leads to chronic muscle weakness, impaired limb function, and even permanent disability. Recent studies suggest muscle residential fibro/adipogenic progenitors (FAPs) can adopt novel beige fat differentiation promoting muscle regeneration. The goal of this study is to define the role of FAP beige adipogenesis in muscle regeneration after VML in a mouse model.Methods Three months old male C57BL/6J mice, PDGFRα-GFP reporter mice, UCP-1 reporter mice, PDGFRα-CREERT/DTA inducible FAP depletion mice and NSG immune-deficient mice were used in this study. Volumetric muscle loss (VML) was created on tibialis anterior (TA) muscle with a punch. To induce FAP beige adipogenesis, Amibegron, a beta 3 adrenergic receptor (B3AR) agonist was administered to mice with I.P. injection. In a separate group, murine and human beige adipogenic FAPs was transplanted to mouse muscle after VML. Limb function was measured with gait analysis at 2 and 6 weeks after VML. Muscle histology and FAP gene expression analysis was also conducted at 2 and 6 weeks after VML.Results After VML, we observed robust proliferation of FAPs in PDGFRα-GFP reporter mice. PDGFRα-CREERT/DTA mice inducible FAP depletion mice showed reduced muscle regeneration after FAPs are depleted, suggesting a positive role of FAP in muscle regeneration after VML. Both Amibegron treatment and beige FAP transplantation significantly improved muscle regeneration and limb function after VML.Conclusion Stimulating FAP beige adipogenesis with B3AR agonists or transplantation of beige adipogenic FAPs could serve as new strategies in treating VML.

Download Full-text

Comparative Effects of Basic Fibroblast Growth Factor Delivery or Voluntary Exercise on Muscle Regeneration after Volumetric Muscle Loss

Bioengineering ◽

10.3390/bioengineering9010037 ◽

2022 ◽

Vol 9 (1) ◽

pp. 37

Author(s):

Caroline Hu ◽

Bugra Ayan ◽

Gladys Chiang ◽

Alex H. P. Chan ◽

Thomas A. Rando ◽

...

Keyword(s):

Cell Proliferation ◽

Endothelial Cell ◽

Growth Factor ◽

Muscle Regeneration ◽

Collagen Scaffold ◽

Voluntary Exercise ◽

Endothelial Cell Proliferation ◽

Fibroblast Growth ◽

Muscle Loss ◽

Volumetric Muscle Loss

Volumetric muscle loss (VML) is associated with irreversibly impaired muscle function due to traumatic injury. Experimental approaches to treat VML include the delivery of basic fibroblast growth factor (bFGF) or rehabilitative exercise. The objective of this study was to compare the effects of spatially nanopatterned collagen scaffold implants with either bFGF delivery or in conjunction with voluntary exercise. Aligned nanofibrillar collagen scaffold bundles were adsorbed with bFGF, and the bioactivity of bFGF-laden scaffolds was examined by skeletal myoblast or endothelial cell proliferation. The therapeutic efficacy of scaffold implants with either bFGF release or exercise was examined in a murine VML model. Our results show an initial burst release of bFGF from the scaffolds, followed by a slower release over 21 days. The released bFGF induced myoblast and endothelial cell proliferation in vitro. After 3 weeks of implantation in a mouse VML model, twitch force generation was significantly higher in mice treated with bFGF-laden scaffolds compared to bFGF-laden scaffolds with exercise. However, myofiber density was not significantly improved with bFGF scaffolds or voluntary exercise. In contrast, the scaffold implant with exercise induced more re-innervation than all other groups. These results highlight the differential effects of bFGF and exercise on muscle regeneration.

Download Full-text

Effects of the tetrahedral framework nucleic acids on the skeletal muscle regeneration in vitro and in vivo

Materials Chemistry Frontiers ◽

10.1039/d0qm00329h ◽

2020 ◽

Vol 4 (9) ◽

pp. 2731-2743

Author(s):

Yang Gao ◽

Tianxu Zhang ◽

Junyao Zhu ◽

Dexuan Xiao ◽

Mei Zhang ◽

...

Keyword(s):

Tissue Regeneration ◽

Muscle Regeneration ◽

Skeletal Muscle Regeneration ◽

Muscle Loss ◽

Degenerative Diseases ◽

Tetrahedral Framework ◽

Volumetric Muscle Loss ◽

Regeneration In Vitro

The challenges associated with muscle degenerative diseases and volumetric muscle loss (VML) emphasizes the prospects of muscle tissue regeneration.

Download Full-text

Volumetric muscle loss leads to permanent disability following extremity trauma

The Journal of Rehabilitation Research and Development ◽

10.1682/jrrd.2014.07.0165 ◽

2015 ◽

Vol 52 (7) ◽

pp. 785-792 ◽

Cited By ~ 72

Author(s):

Benjamin T. Corona ◽

Jessica C. Rivera ◽

Johnny G. Owens ◽

Joseph C. Wenke ◽

Christopher R. Rathbone

Keyword(s):

Muscle Loss ◽

Permanent Disability ◽

Volumetric Muscle Loss ◽

Extremity Trauma

Download Full-text

Losartan administration reduces fibrosis but hinders functional recovery after volumetric muscle loss injury

Journal of Applied Physiology ◽

10.1152/japplphysiol.00689.2014 ◽

2014 ◽

Vol 117 (10) ◽

pp. 1120-1131 ◽

Cited By ~ 37

Author(s):

Koyal Garg ◽

Benjamin T. Corona ◽

Thomas J. Walters

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Muscle Function ◽

Collagen Type ◽

Force Production ◽

Collagen Type I ◽

Type I ◽

Muscle Loss ◽

Muscle Injuries ◽

Volumetric Muscle Loss

Losartan is a Food and Drug Administration approved antihypertensive medication that is recently emerging as an antifibrotic therapy. Previously, losartan has been successfully used to reduce fibrosis and improve both muscle regeneration and function in several models of recoverable skeletal muscle injuries, such as contusion and laceration. In this study, the efficacy of losartan treatment in reducing fibrosis and improving regeneration was determined in a Lewis rat model of volumetric muscle loss (VML) injury. VML has been defined as the traumatic or surgical loss of skeletal muscle with resultant functional impairment. It is among the top 10 causes for wounded service members to be medically retired from the military. This study shows that, after several weeks of recovery, VML injury results in little to no muscle regeneration, but is marked by persistent inflammation, chronic upregulation of profibrotic markers and extracellular matrix (i.e., collagen type I), and fat deposition at the defect site, which manifest irrecoverable deficits in force production. Losartan administration at 10 mg·kg−1·day−1was able to modulate the gene expression of fibrotic markers and was also effective at reducing fibrosis (i.e., the deposition of collagen type I) in the injured muscle. However, there were no improvements in muscle regeneration, and deleterious effects on muscle function were observed instead. We propose that, in the absence of regeneration, reduction in fibrosis worsens the ability of the VML injured muscle to transmit forces, which ultimately results in decreased muscle function.

Download Full-text

A porous collagen‐GAG scaffold promotes muscle regeneration following volumetric muscle loss injury

Wound Repair and Regeneration ◽

10.1111/wrr.12768 ◽

2019 ◽

Vol 28 (1) ◽

pp. 61-74

Author(s):

Adriana C. Panayi ◽

Lucindi Smit ◽

Nicole Hays ◽

Kodi Udeh ◽

Yori Endo ◽

...

Keyword(s):

Muscle Regeneration ◽

Muscle Loss ◽

Volumetric Muscle Loss

Download Full-text

A Porcine Urinary Bladder Matrix Does Not Recapitulate the Spatiotemporal Macrophage Response of Muscle Regeneration after Volumetric Muscle Loss Injury

Cells Tissues Organs ◽

10.1159/000447582 ◽

2016 ◽

Vol 202 (3-4) ◽

pp. 189-201 ◽

Cited By ~ 10

Author(s):

Amit Aurora ◽

Benjamin T. Corona ◽

Thomas J. Walters

Keyword(s):

Urinary Bladder ◽

Muscle Fiber ◽

Muscle Regeneration ◽

De Novo ◽

Muscle Loss ◽

Macrophage Response ◽

Urinary Bladder Matrix ◽

Volumetric Muscle Loss ◽

Fibrotic Scar ◽

Muscle Fiber Regeneration

Volumetric muscle loss (VML) results in irrecoverable loss of muscle tissue making its repair challenging. VML repair with acellular extracellular matrix (ECM) scaffolds devoid of exogenous cells has shown improved muscle function, but limited de novo muscle fiber regeneration. On the other hand, studies using minced autologous and free autologous muscle grafts have reported appreciable muscle regeneration. This raises the fundamental question whether an acellular ECM scaffold can orchestrate the spatiotemporal cellular events necessary for appreciable muscle fiber regeneration. This study compares the macrophage and angiogenic responses including the remodeling outcomes of a commercially available porcine urinary bladder matrix, MatriStem™, and autologous muscle grafts. The early heightened and protracted M1 response of the scaffold indicates that the scaffold does not recapitulate the spatiotemporal macrophage response of the autograft tissue. Additionally, the scaffold only supports limited de novo muscle fiber formation and regressing vessel density. Furthermore, scaffold remodeling is accompanied by increased presence of transforming growth factor and α-smooth muscle actin, which is consistent with remodeling of the scaffold into a fibrotic scar-like tissue. The limited muscle formation and scaffold-mediated fibrosis noted in this study corroborates the findings of recent studies that investigated acellular ECM scaffolds (devoid of myogenic cells) for VML repair. Taken together, acellular ECM scaffolds when used for VML repair will likely remodel into a fibrotic scar-like tissue and support limited de novo muscle fiber regeneration primarily in the proximity of the injured musculature. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel

Download Full-text

Exploratory study on the effect of osteoactivin on muscle regeneration in a rat volumetric muscle loss model

PLoS ONE ◽

10.1371/journal.pone.0175853 ◽

2017 ◽

Vol 12 (4) ◽

pp. e0175853 ◽

Cited By ~ 4

Author(s):

Jinjin Ma ◽

Andrew R. Baker ◽

Anthony Calabro ◽

Kathleen A. Derwin

Keyword(s):

Muscle Regeneration ◽

Exploratory Study ◽

Muscle Loss ◽

Loss Model ◽

Volumetric Muscle Loss

Download Full-text

Role of Vibrations in Orthodontics: A Review

Orthodontic Journal of Nepal ◽

10.3126/ojn.v8i2.23072 ◽

2018 ◽

Vol 8 (2) ◽

pp. 50-54

Author(s):

Varun Goyal ◽

Raj Kumar Singh ◽

Nishant Gupta ◽

Gurkeerat Singh ◽

Ashima Relhan

Keyword(s):

Muscle Regeneration ◽

Joint Pain ◽

Orthodontic Treatment ◽

Tooth Movement ◽

Root Resorption ◽

Treatment Time ◽

Bone Remodelling ◽

Muscle Loss ◽

Vibration Therapy

Long treatment time has been a deterrent for the patients for pursuing orthodontic treatment. Orthodontist from time immemorial have been trying different methods for reducing the treatment time. It has been documented in literature that vibration therapy helps in bone remodelling and muscle regeneration as demonstrated in cases of osteoporosis, muscle loss and joint pain. Using the similar approach orthodontist from different era have tried to accelerate the tooth movement using different methods. This article summarises the efforts of different clinicians and their approaches to achieve reduced orthodontic treatment time as well as reducing the discomfort, pain and root resorption using pulsations and vibrations.

Download Full-text