scholarly journals MMP inhibition as a potential method to augment the healing of skeletal muscle and tendon extracellular matrix

2013 ◽  
Vol 115 (6) ◽  
pp. 884-891 ◽  
Author(s):  
Max E. Davis ◽  
Jonathan P. Gumucio ◽  
Kristoffer B. Sugg ◽  
Asheesh Bedi ◽  
Christopher L. Mendias

The extracellular matrix (ECM) of skeletal muscle and tendon is composed of different types of collagen molecules that play important roles in the transmission of forces throughout the body, and in the repair and regeneration of injured tissues. Fibroblasts are the primary cells in muscle and tendon that maintain, repair, and modify the ECM in response to mechanical loading, injury, and inactivity. Matrix metalloproteinases (MMPs) are enzymes that digest collagen and other structural molecules, which are synthesized and excreted by fibroblasts. MMPs are required for baseline ECM homeostasis, but disruption of MMP regulation due to injury or disease can alter the normal ECM architecture and prevent proper force transmission. Chronic injuries and diseases of muscles and tendons can be severely debilitating, and current therapeutic modalities to enhance healing are quite limited. This review will discuss the mechanobiology of MMPs, and the potential use of MMP inhibitors to improve the treatment of injured and diseased skeletal muscle and tendon tissue.

Author(s):  
Chi Zhang ◽  
Yingxin Gao

Skeletal muscle has a complex hierarchical structure which is mainly composed of myofibers and the surrounding extracellular matrix (ECM) including endomysium, perimysium, and epimysium. Myofibers are long, cylindrical, multinucleated cells composed of repeating sarcomeres, which are basic functional units for skeletal muscle contraction. In order to produce body movement, the force generated by myofiber has to be transmitted from individual fiber to the tendon. The commonly accepted site for force transmission is the myotendinous junction (MTJ) where the myofibers connect to the tendon. However, the myofibers mainly end within the muscle fascicles without reaching the MTJ in many muscles, in which case the force has to be transmitted laterally to adjacent fiber through shear and to the tendon eventually.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ching-Yan Chloé Yeung ◽  
Erwin M. Schoof ◽  
Michal Tamáš ◽  
Abigail L. Mackey ◽  
Michael Kjaer

Abstract Background Fibroblasts are the powerhouses responsible for the production and assembly of extracellular matrix (ECM). Their activity needs to be tightly controlled especially within the musculoskeletal system, where changes to ECM composition affect force transmission and mechanical loading that are required for effective movement of the body. Extracellular vesicles (EVs) are a mode of cell-cell communication within and between tissues, which has been largely characterised in cancer. However, it is unclear what the role of healthy fibroblast-derived EVs is during tissue homeostasis. Methods Here, we performed proteomic analysis of small EVs derived from primary human muscle and tendon cells to identify the potential functions of healthy fibroblast-derived EVs. Results Mass spectrometry-based proteomics revealed comprehensive profiles for small EVs released from healthy human fibroblasts from different tissues. We found that fibroblast-derived EVs were more similar than EVs from differentiating myoblasts, but there were significant differences between tendon fibroblast and muscle fibroblast EVs. Small EVs from tendon fibroblasts contained higher levels of proteins that support ECM synthesis, including TGFβ1, and muscle fibroblast EVs contained proteins that support myofiber function and components of the skeletal muscle matrix. Conclusions Our data demonstrates a marked heterogeneity among healthy fibroblast-derived EVs, indicating shared tasks between EVs of skeletal muscle myoblasts and fibroblasts, whereas tendon fibroblast EVs could play a fibrotic role in human tendon tissue. These findings suggest an important role for EVs in tissue homeostasis of both tendon and skeletal muscle in humans.


2020 ◽  
Vol 142 (10) ◽  
Author(s):  
Seungman Park ◽  
Wei-Hung Jung ◽  
Matthew Pittman ◽  
Junjie Chen ◽  
Yun Chen

Abstract Cells sense biophysical cues in the micro-environment and respond to the cues biochemically and biophysically. Proper responses from cells are critical to maintain the homeostasis in the body. Abnormal biophysical cues will cause pathological development in the cells; pathological or aging cells, on the other hand, can alter their micro-environment to become abnormal. In this minireview, we discuss four important biophysical cues of the micro-environment—stiffness, curvature, extracellular matrix (ECM) architecture and viscosity—in terms of their roles in health, aging, and diseases.


2017 ◽  
Vol 26 (2) ◽  
pp. 171-179 ◽  
Author(s):  
Jeffrey J. Dueweke ◽  
Tariq M. Awan ◽  
Christopher L. Mendias

Eccentric-contraction-induced skeletal muscle injuries, included in what is clinically referred to as muscle strains, are among the most common injuries treated in the sports medicine setting. Although patients with mild injuries often fully recover to their preinjury levels, patients who suffer moderate or severe injuries can have a persistent weakness and loss of function that is refractory to rehabilitation exercises and currently available therapeutic interventions. The objectives of this review were to describe the fundamental biophysics of force transmission in muscle and the mechanism of muscle-strain injuries, as well as the cellular and molecular processes that underlie the repair and regeneration of injured muscle tissue. The review also summarizes how commonly used therapeutic modalities affect muscle regeneration and opportunities to further improve our treatment of skeletal muscle strain injuries.


Leonardo ◽  
2015 ◽  
Vol 48 (3) ◽  
pp. 270-271
Author(s):  
Miranda D. Grounds

The contraction of specialized skeletal muscle cells results in classic movements of bones and other parts of the body that are vital for life. There is exquisite control over the movement of diverse types of muscles. This paper indicates the way in which skeletal muscles (myofibres) are formed; then factors that contribute to generating the movement are outlined: these include the nerve, sarcomeres, cytoskeleton, cell membrane and the extracellular matrix. The factors controlling the movement of mature myofibres in 3-dimensional tissues in vivo are vastly more complex than for tissue cultured immature muscle cells in an artificial in vitro environment.


Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 148 ◽  
Author(s):  
Khurshid Ahmad ◽  
Eun Lee ◽  
Jun Moon ◽  
So-Young Park ◽  
Inho Choi

The skeletal muscle provides movement and support to the skeleton, controls body temperature, and regulates the glucose level within the body. This is the core tissue of insulin-mediated glucose uptake via glucose transporter type 4 (GLUT4). The extracellular matrix (ECM) provides integrity and biochemical signals and plays an important role in myogenesis. In addition, it undergoes remodeling upon injury and/or repair, which is also related to insulin resistance (IR), a major cause of type 2 diabetes (T2DM). Altered signaling of integrin and ECM remodeling in diet-induced obesity is associated with IR. This review highlights the interweaving relationship between the ECM, IR, and skeletal muscle. In addition, the importance of the ECM in muscle integrity as well as cellular functions is explored. IR and skeletal muscle ECM remodeling has been discussed in clinical and nonclinical aspects. Furthermore, this review considers the role of ECM glycation and its effects on skeletal muscle homeostasis, concentrating on advanced glycation end products (AGEs) as an important risk factor for the development of IR. Understanding this complex interplay between the ECM, muscle, and IR may improve knowledge and help develop new ideas for novel therapeutics for several IR-associated myopathies and diabetes.


Author(s):  
Khurshid Ahmad ◽  
Inho Choi ◽  
Yong-Ho Lee

The skeletal muscle provides movement and support to the skeleton, controls body temperature, and regulates the glucose level within the body. This is the core tissue of insulin-mediated glucose uptake via glucose transporter type 4 (GLUT4). The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes, and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.


Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 18-20
Author(s):  
Shuhei Tsuchiya

Osseointegration can be defined as a direct connection, both structural and functional, between living bone and the surface of an artificial implant. Indeed, the word comes from the Greek term for 'bone' and 'to make whole'. In dentistry, once dental implants are placed, the body will react with osseointegration, enabling the implants to become a permanent part of the jaw. There are many benefits to this type of implant, compared with traditional tooth replacement options, not least that dental implants mimic the strength and functionality of a natural tooth. Dr Shuhei Tsuchiya is a researcher based in the Division of Oral and Maxillofacial Surgery at Nagoya University, Japan, who is interested in a range of areas, including regenerative medicine and the extracellular matrix. One of his key preoccupations, though, is shedding light on osseointegration. He and his team are working to unravel the mysteries of the mechanism.


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