The Centre for Bone and Muscle Health’s faculty members and researchers investigate bone and muscle health through diverse lenses; But how is it all connected? This image visualizes frequently occurring keywords within the last five years. The larger the circle, the more frequently the word appears. They are then linked to keywords that have been used together and thus a map is created to show how all of our research is interconnected.
Neuromuscular function in growth and development
Ongoing studies are designed to answer the following questions: how does exercise and training affect the body and how does growth affect child performance and health? The goal of these studies is to examine muscle activation, muscle performance and the effect of growth and development on muscle activation and performance in children.
Healthy children and adult participants are tested on muscle performance in terms of strength, explosive strength, endurance and fatigue. Electromyography (EMG) is used to examine muscle activation and ultrasounds is used to examine muscle size. Most exercise-related research is focused on adults, which means that recommendations for training or physiotherapy for children are derived from adult data. These studies aim to collect new data, resulting in updated and relevant recommendations for children.
Nutrition, pain and periodontal wellness
Research by our group and others are increasingly demonstrating a link between diet and periodontal health, with specific foods and nutrients being associated with better healing and recovery after non-surgical interventions such as a ‘deep cleaning’. For example, higher intakes of fruits and vegetables, as well as vitamin C, are associated with better healing and periodontal outcomes after such interventions. This is important as periodontal disease, if left untreated, results in tooth loss. In turn, individuals with fewer teeth can find it difficult to consume a varied diet, rich in foods that provide important nutrients and bioactives for overall health. This can set a trajectory for risk of chronic diseases that are associated with a poor diet. Interestingly, a common reason why individuals do not seek periodontal treatment is due to fear of anticipated pain with a periodontal procedure. Thus, a recent study by our team investigated whether anticipated pain of a patient predicted actual pain experienced, to provide patients with evidence-based information regarding actual pain experienced, and to help prevent patient avoidance of periodontal procedures that promote wellness.
Optimizing bone structure and strength using diet
In terms of diet and bone strength, research in the developmental origins of health and disease and also during aging is an active focus of our research program. “Nutritional programming” is the term used to describe this phenomenon in which diet, during earliest stages of life, sets a trajectory for improved or compromised bone structure and strength at later stages of life. Aging also presents a unique opportunity for nutrients and food components to modulate bone cell activity and structure, making the skeleton more resistant to age-related fractures. Using well-characterized preclinical models, our research team has studied how calcium and vitamin D as well as bioactives such as flavonoids in tea, soy and citrus; flaxseed lignans; and fatty acids result in nutritional programming effects on bone development or support aging bone. These studies have also included consideration of sex-specific responses.
Muscle wasting and disease
The Fajardo Research Team explores the cellular basis of muscle atrophy in conditions of muscle unloading and disease. We employ several mouse models including ground-based (ie. tenotomy) and spaceflight models (supported by NASA) of muscle atrophy to uncover potential countermeasures that prevent muscle loss. In addition, we study the mdx mouse model of Duchenne muscular dystrophy, which is a severe a debilitating disease leading to early mortality. Unifying these models, our lab focuses on glycogen synthase kinase 3 and various calcium regulatory proteins. Led by: Holt Messner, PhD student, Kennedy Whitley, MSc student, Riley Cleverdon, MSc student, Emily Copeland, MSc student, Ryan Baranowski, MSc student
Bone response to exercise and training
Dr. Klentrou’s NSERC funded research involves a systematic examination of the responses, variation, and adaptations of bone tissue to multiple stressors, including exercise and dietary (energy) restriction. We monitor bone adaptation by means of serum biochemical markers that can detect changes in the metabolic status of bone, allowing the investigation of the acute and chronic effects of exercise on bone remodeling. The central hypothesis is that there is an age/maturity and sex dependent, optimal range of exercise intensity and duration, as well as level and content of dietary (energy) intake, that favor the balance between bone formation and bone resorption via endocrine and/or paracrine factors triggered by muscle that act directly on osteoblasts.
Wnt β-catenin signal transduction pathway is a conserved pathway that is critical for bone formation. Sclerostin is an osteokine (i.e., bone specific cytokine) secreted by osteocytes that acts as an inhibitor of Wnt signaling, thus downregulating bone formation. Recently, our lab has worked on assessing the response of sclerostin to acute exercise and training. The first series of experiments assessed the acute response (5 min – 24h) of sclerostin in crude serum post-plyometric exercise in both male and female participants who were either pre-pubertal children (~7-12y), adolescents (13-18y), young adults (19-25y) or older adults (>50y). Interestingly, despite knowing that mechanical loading decreases sclerostin expression, we identified that in general, adults have a large increase in following both high impact and high-intensity low impact exercise. In contrast, we also found that, in spite of having a lower resting concentration, children do not present this post-exercise increase in sclerostin. However, children who have excess adiposity show a large increase in sclerostin, similar to adults. Furthermore, when we monitored elite female rowers across a training year, we showed that when training load (intensity and volume) was highest, serum sclerostin was the highest and during tapering (low training load), serum sclerostin was the lowest. The fluctuation in sclerostin paralleled changes in inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin 6 and 1β. Taken together, these data suggest that children are protected from osteoclastogenesis and sclerostin mediated inhibition of Wnt signaling following exercise and that periods of intense training can lead to inhibited Wnt signaling through the increase in sclerostin, potentially mediated by inflammation. Additionally, we have recently shown that the acute post-exercise increase in sclerostin appears to be mediated by TNF-α as well. Our next step is to elucidate mechanisms of cellular crosstalk, specifically as it pertains to bone, inflammation and adipose tissue. We plan to address sex differences and changes with growth and development (children vs. young adults) of the molecular and cellular regulators of the bone response to exercise and training using modern laboratory approaches. Specifically, we now focus on the study of extracellular vesicles, including microvesicles and exosomes, as a mechanism of cellular crosstalk.
Nutritional strategies to improve recovery in young athletes
Elite athletes’ training is often periodized. Periodization involves instances of increased volume and/or intensity (~1-week), followed by a tapering component prior to competition. During intense training, nutrition to support and maintain recovery prior to the next training session is imperative. This is especially important in youth athletes where nutrition must also sustain and support their growth and development. Understanding how to enhance fuel and tissue recovery or attenuate tissue trauma during an intense period of training in athletic children is essential to maximize the training response while supporting growth and development, and at the same time, mitigating any form of overtraining. The long-term objective of our research is to investigate the effects of protein supplementation combined with exercise on muscle damage and inflammation, and on exercise performance in young athletes. In the first phase of this research, we examined whether whey protein supplementation following an intense exercise session can enhances exercise performance, bone turnover and affects muscle damage and inflammation. In the second phase of this research we propose to examine whether the consumption of three daily doses of Greek yogurt, eaten immediately following exercise training, mid-day and before bedtime during an intense, 1-week training period, will increase bone turnover and attenuate muscle damage, inflammation and potential performance decrement in youth soccer athletes. Whole food dairy products, such as Greek yogurt, are high quality, nutrient-dense post-exercise snacks, high in protein and other ingredients to optimize the recovery process. Casein, the main dairy protein, which Greek yogurt is primarily composed of, is absorbed slower than other dairy-derived proteins (e.g., whey), and can provide a sustained positive amino-acid flux for several hours after ingestion, permitting the stimulus for muscle protein synthesis over a prolonged period time. Thus, Greek yogurt may be the ideal post-workout snack, especially during periods of increased training. The results of this research will provide nutritional and training recommendations for young athletes, which can be smoothly implemented by athletes, parents and coaches. Given the scant available data on protein requirements for youth, especially athletes, the results will greatly benefit the nutritional supplements industry. Finally, this study will provide a basis for informed protein intake recommendations for active Canadian youth, leading a healthy lifestyle.
Biomechanical and Neurophysiological Factors Contributing to Low Back Pain
Estimates suggest that over 80% of the population will experience low back pain (LBP) at some point in their lives. Further, most cases of LBP are characterized as ‘non-specific’, meaning that they have no specific underlying structural deformity causing the reported pain. One potential means to discriminate different subgroups within the heterogenous condition of LBP is through the investigation of spine motor control. Motor control refers to all of the sensory and motor processes associated with the control of the spine and has been targeted as a core element of many interventions for LBP. Dr. Beaudette’s NSERC funded research program is designed to use novel methods to understand the biomechanical and neurophysiological factors contributing to the control of spine movement. Dr. Beaudette’s lab uses research tools like 3D motion capture and electromyography (EMG) to develop and assess novel objective measures of spine motor function. In many cases, these measures are integrated into a data science framework to understand how different movement patterns associate with LBP, how different anatomical elements contribute to the maintenance of spine stability, and how targeted sensory feedback and rehabilitation/training programs can be used to reinforce specific motor patterns.
Use of plant-derived chemicals to counteract muscle insulin resistance
Skeletal muscle is an important target tissue of insulin and plays an important role in maintaining blood glucose homeostasis.
In skeletal muscle, insulin action is initiated by binding of insulin to its receptor leading to downstream tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), activation of phosphatidylinositol-3 kinase (PI3K), protein kinase B/Akt, and GLUT4 glucose transporter translocation from an intracellular storage site to plasma membrane allowing an increase in glucose uptake.
Impairments in the IRS-1-PI3K-Akt signaling cascade result in insulin resistance and type 2 diabetes mellitus (T2DM). Nutrient overload, elevated free fatty acid (FFA) levels, often seen in obesity, contribute to insulin resistance and are a major risk factor for the development of T2DM.
We use skeletal muscle cells in vitro as well as in vivo animal models of insulin resistance and T2DM. Our aim is to elucidate the signaling pathways that contribute to the pathogenesis of insulin resistance and diabetes. In addition, we investigate the anti-diabetic properties of plant-derived chemicals.
Our goal is to find plant-derived compounds that could be used to prevent and/or treat insulin resistance and diabetes.
Muscle metabolism as it relates to obesity and diabetes
Skeletal muscle accounts for 40-50% of the mammalian body and is a highly metabolic tissue that expends a tremendous amount of energy on a daily basis both at rest and during exercise. Knowing this, our lab aims to target skeletal muscle energy expenditure to combat obesity and diabetes by activating a process called muscle-based thermogenesis. By uncoupling the calcium pump, our cells will increase their energy expenditure and therefore has the potential to combat the deleterious effects of excess caloric intake and physical inactivity. The Fajardo Research Team is currently investigating novel ways to increase the expression of sarcolipin, a well-known uncoupler of the calcium pump. In addition, they are interested in the discovery and characterization of other potential uncouplers that may act like sarcolipin, such as neuronatin. Neuronatin has been shown to play a role in regulating SERCA function in the brain. Our lab is specifically examining whether it can uncouple SERCA in muscle as well as other mammalian tissues. Led by: Mia Geromella, MSc student, Jessica Braun, MSc student, Briana Hockey, MSc student, Jisook Ryoo, BSc student
Dietary strategy to improve skeletal muscle form and function in Barth syndrome
Barth syndrome is a rare yet incurable X-linked (male-specific) genetic disease that affects the protein tafazzin. Tafazzin is an important enzyme responsible for synthesizing cardiolipin, an important lipid critical for mitochondrial form and function. Dysfunctional mitochondria due to mutations to tafazzin, as seen in Barth syndrome, result in an enlarged heart, a weakened immune system, and exercise intolerance. As there is no cure for Barth syndrome, current treatment strategies have focused on reducing symptoms and preventing complications associated with heart and immune dysfunction. To date, there has been limited research on improving skeletal muscle function, with interventions focused on exercise. However, previous cell culture research has shown therapeutic potential of linoleic acid, an important precursor for proper cardiolipin synthesis, in reversing the hallmark cellular impacts of Barth syndrome on mitochondrial form and function. As such, there is an opportunity to improve skeletal muscle weakness and exercise intolerance using an alternative therapy, specifically dietary supplementation of linoleic acid. Thus, our lab is investigating the potential for dietary linoleic acid to reverse or prevent mitochondrial dysfunction and improve or preserve skeletal muscle form and function using a preclinical model of Barth syndrome.
Work Shouldn’t Hurt
All too often, people leave work at the end of the day feeling tired and suffering from aches or pains. This not only influences performance at work, but quality of life at home. Musculoskeletal disorders (MSDs) are the single most frequent reason why people miss work and the associated costs to our healthcare system is alarming. Almost all work tasks require use of the upper extremity, so it is not surprising that injury rates are highest in this region of the body. While our understanding of injury mechanisms has improved over the past few decades, the prevalence of upper extremity injuries remains troubling. Research in the Neuromechanics and Ergonomics Lab at Brock University uses cutting edge robotics, motion capture and muscle activity technology to quantify upper extremity workplace demands to provide guidelines that make the workplace safer.
Posttranlational Myosin Phosphorylation
Our skeletal muscle mass is critical for survival from a mechanical, metabolic and thermogenic perspective. The overall theme of our work is the study of how the posttranslational modification of the myosin motor protein by phosphorylation influences these respective processes. Individual muscle fibers, particularly fast twitch muscle fibers, contain an enzyme called myosin light chain kinase the catalytic activity of which is increased whenever these fibers contract. This enzyme catalyzes a reaction in which a phosphate moiety is transferred from adenosinetriphosphate (ATP) to a myosin subunit known as the regulatory light chain. This kinase mediated phosphorylation of the light chain improves myosin motor ability to cause “potentiation”, i.e. the transient increase in muscle force caused by contraction. As a result, skeletal muscles with myosin phosphorylation display higher levels of work, power and economy than do muscles without myosin phosphorylation. Interestinly, it seems possible that this molecular mechanism evolved to help fast twitch muscles resist the performance-robbing effects of fatigue. In addition, we are investigating how myosin phosphorylation participates in the regulation of skeletal muscle heat output or thermogenesis. We are studying the ability of myosin phosphorylation to influence resting muscle thermogenesis when mice are fed surplus calories as well as shivering thermogenesis when mice are exposed to cold. Both of these types of studies will employ our line of genetically modified “knock out” mice that do not contain the skeletal myosin light chain kinase enzyme and thus do not have the ability to phosphorylate myosin. We expect that these studies will help identify the biological role of myosin light chain phosphorylation in fast and slow skeletal muscle fibers.
Cardiac calcium regulation
Cardiac muscle is vital. With each heartbeat, calcium is sent out to the muscle cytosol activating the necessary muscle contraction that pumps blood to our bodies. After contraction, comes relaxation, which is an important part of the cardiac cycle that allows for refilling of the heart with blood. To elicit muscle relaxation, the cardiac muscle calcium pump transports calcium back into the calcium reservoir called the sarcoplasmic reticulum. In conditions of heart failure and numerous cardiomyopathies (ie. dilated cardiomyopathy and arrhythmogenic cardiomyopathy) the calcium pump function is severely impaired. The Fajardo Research Team aims to improve calcium pump function in these diseased states to try and drastically improve the physiological outcomes. Led by: Sophie Hamstra, MSc student