Impact of age on host responses to diet-induced obesity: Development of joint damage and metabolic set points

Collins, Kelsey H.; MacDonald, Graham Z.; Hart, David A.; Seerattan, Ruth A.; Rios, Jaqueline Lourdes; Reimer, Raylene A.; Herzog, Walter

doi:10.1016/j.jshs.2019.06.004

Cited by 12 publications

(12 citation statements)

References 44 publications

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“…These models have been shown to successfully induce OA-like joint degeneration [81][82][83] mainly driven by low-grade inflammation [80]. In line with other studies, age has been shown as a contributing factor in dietinduced OA severity [84]. It is interesting, however, that individuals from the same species have been reported to display distinct obesity phenotypes in response to dietinduced metabolic disturbance, and that their susceptibility or resistance can be associated with severity of OA-like knee damage [81,85].…”

Section: Models Of Oa and Cartilage Damagesupporting

confidence: 60%

Understanding cartilage protection in OA and injury: a spectrum of possibilities

Masson

Krawetz

2020

BMC Musculoskelet Disord

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Background: Osteoarthritis (OA) is a prevalent musculoskeletal disease resulting in progressive degeneration of the hyaline articular cartilage within synovial joints. Current repair treatments for OA often result in poor quality tissue that is functionally ineffective compared to the hyaline cartilage and demonstrates increased failure rates posttreatment. Complicating efforts to improve clinical outcomes, animal models used in pre-clinical research show significant heterogeneity in their regenerative and degenerative responses associated with their species, age, genetic/epigenetic traits, and context of cartilage injury or disease. These can lead to variable outcomes when testing and validating novel therapeutic approaches for OA. Furthermore, it remains unclear whether protection against OA among different model systems is driven by inhibition of cartilage degeneration, enhancement of cartilage regeneration, or any combination thereof. Main text: Understanding the mechanistic basis underlying this context-dependent duality is essential for the rational design of targeted cartilage repair and OA therapies. Here, we discuss some of the critical variables related to the cross-species paradigm of degenerative and regenerative abilities found in pre-clinical animal models, to highlight that a gradient of regenerative competence within cartilage may exist across species and even in the greater human population, and likely influences clinical outcomes. Conclusions: A more complete understanding of the endogenous regenerative potential of cartilage in a species specific context may facilitate the development of effective therapeutic approaches for cartilage injury and/or OA.

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Section: Models Of Oa and Cartilage Damagesupporting

confidence: 60%

Understanding cartilage protection in OA and injury: a spectrum of possibilities

Masson

Krawetz

2020

BMC Musculoskelet Disord

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“…Adult onset obesity is a risk factor for knee OA (Courties et al, 2019;D.A. Hart et al Godziuk et al, 2018), but obesity arising prior to skeletal maturity may not yield the same results with regard to OA development., This conclusion is based on results from a preclinical rat model (Collins et al, 2020) where onset of adult diet-induced obesity led to knee joint damage, but induction of obesity in the post-weaning period did not lead to joint damage. Thus, onset of obesity and its consequences at an early age may be included in establishing the biomechanical set point of a joint as the individual reaches maturation, thus preventing joint damage rather than inducing larger loads than the joint developed to resist after the fact in the adult.…”

Section: The Role Of Obesitymentioning

confidence: 99%

The instrumented sheep knee to elucidate insights into osteoarthritis development and progression: A sensitive and reproducible platform for integrated research efforts

Hart

Martin

Scott

et al. 2021

Clinical Biomechanics

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Background: Osteoarthritis of the knee is a very common condition that has been difficult to treat. The majority of cases are considered idiopathic. Much research effort remains focused on biology rather than the biomechanics of such joints. Some new methods were developed and validated to better appreciate the subtleties of the biomechanical integrity of joints, and how changes in biomechanics can contribute to osteoarthritis. Methods: Over the past 15 years our lab has enhanced the sensitivity of the assessment of knee biomechanics of an instrumented, trained large animal model (sheep) of osteoarthritis and integrated the findings with biological and histological assessments. These new methods include gait analysis before and after injury followed by robotic validation post-sacrifice, and more recently using Fibre Bragg Grating sensors to detect alterations in cartilage stresses. Results: A review of the findings obtained with this model are presented. The findings indicate that sheep, like humans, exhibit individual characteristics. They also indicate that joint kinetics, rather than kinematics may better define the alterations induced by injury. With the addition of Fibre Bragg Grating sensors, it has been possible to measure with good accuracy, alterations to cartilage stresses following a controlled knee injury. Interpretation: Using this model as Proof of Concept, this sheep system can now be viewed as a sensitive platform to address many questions related to risk for development of idiopathic osteoarthritis of the human knee, the efficacy of potential interventions to correct biomechanical disruptions, and how joint biomechanics and biology are integrated during aging.

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“…Furthermore, while obese children/adolescents and adults both appear to respond to fibre diet interventions similarly (discussed in [34,35]), it is also likely that becoming obese during maturation and onset of puberty may impart unique aspects to obesity compared to adults, but details in this regard are still unclear [5]. While some obesity-risk may be inherited via epigenetic mechanisms from either parent (discussed in [15,36]), whether unique epigenetic mechanisms arise with childhood obesity prior to puberty or skeletal and physiological maturity, whether there are sex-specific epigenetic changes occurring, and whether the epigenetic changes occurring as a consequence of childhood obesity differ from those arising during adult obesity, largely remain the subject of current research.…”

Section: The Critical Issue Of Why the Obesity Epidemic Is Happeningmentioning

confidence: 99%

“…Unfortunately, other parts of the world are rapidly catching up to these disturbing statistics. Even more disturbing is the fact that childhood obesity is also rising rapidly (discussed in [5][6][7]), findings that portend early development of severe health risks in young populations. Some organizations have supported the designation of obesity as a disease, but whether it is a disease or a condition that has consequences for subsequent increased risk for diseases such as type 2 diabetes, cardiovascular disease, cognitive decline, and development and progression of musculoskeletal diseases such as osteoarthritis, sarcopenia, and bone diseases, remains to be clarified.…”

Section: Introduction 1the Current Situationmentioning

confidence: 99%

Obesity, the Obesity Epidemic, and Metabolic Dysfunction: The Conundrum Presented by the Disconnect between Evolution and Modern Societies

Hart¹

2021

JBiSE

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Currently, there is an obesity epidemic in the developed world, with both adults and children being affected. The consequences of this epidemic on health and health outcomes have impact at multiple levels, and it is increasing. The basis for this epidemic, which appears to have emerged with significance ~40 -50 years ago, is unknown but is believed by many to have much of its basis in poor diets and inactivity/sedentary behaviour. Analysis of the human genome has revealed >100 loci which exhibit risk for development of obesity. Why there are so many loci, and how they benefited humans evolutionarily are unknown. In spite of these limitations, there are urgent needs for effective short-term interventions to assist those with obesity, as well as longer-term needs to effectively prevent development of obesity. For the former, personalized exercise programs, use of prebiotics, optimal nutrition and surgical interventions can be effective for some individuals but more interventions that address cause are also needed. For longer term solutions more detailed genetic and epigenetic understanding of risk will be required. An attractive speculation is that the genomic risk factors for obesity (>100 identified) have been retained evolutionarily to address acute metabolic needs and current conditions have converted such risks to a chronic state, making reversal more difficult and with more consequences, including possible epigenetic modifications of risk genes. Other contributing factors to chronic obesity could also relate to chemical disruptors in the environment over the past 50+ years which may impact metabolic regulation via the established risk genomic risk factors or new variants. Therefore, to

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Impact of age on host responses to diet-induced obesity: Development of joint damage and metabolic set points

Cited by 12 publications

References 44 publications

Understanding cartilage protection in OA and injury: a spectrum of possibilities

Understanding cartilage protection in OA and injury: a spectrum of possibilities

The instrumented sheep knee to elucidate insights into osteoarthritis development and progression: A sensitive and reproducible platform for integrated research efforts

Obesity, the Obesity Epidemic, and Metabolic Dysfunction: The Conundrum Presented by the Disconnect between Evolution and Modern Societies

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