Removal of the infrapatellar fat pad and associated synovium benefits female guinea pigs in the Dunkin Hartley model of idiopathic osteoarthritis.

Background: Several tissues contribute to the onset and advancement of knee osteoarthritis (OA). One tissue type that is worthy of closer evaluation, particularly in the context of sex, is the infrapatellar fat pad (IFP). We previously demonstrated that removal of the IFP had short-term beneficial effects for a cohort of male Dunkin-Hartley guinea pigs.

Comparison of two point of care lactate instruments in guinea pigs ().

Background: Lactate measurements have been utilized as diagnostic and prognostic tools for a variety of veterinary species. Reference intervals for lactate have not been published or validated in guinea pigs.

Methods: Whole blood from 48 anesthetized laboratory guinea pigs (46 Dunkin Hartley [38 males, eight females]; two Strain 13 [two males]) was analyzed using two point of care instruments (iSTAT and Lactate Plus).

Non-transgenic guinea pig strains exhibit divergent age-related changes in hippocampal mitochondrial respiration.

Aim: Alzheimer's disease (AD) is the most common form of dementia. However, while 150+ animal models of AD exist, drug translation from preclinical models to humans for treatment usually fails. One factor contributing to low translation is likely the absence of neurodegenerative models that also encompass the multi-morbidities of human aging.

Immunization against nucleus pulposus antigens to accelerate degenerative disc disease in a rabbit model.

Low back pain poses a significant societal burden, with progressive intervertebral disc degeneration (IDD) emerging as a pivotal contributor to chronic pain. Improved animal models of progressive IDD are needed to comprehensively investigate new diagnostic and therapeutic approaches to managing IDD. Recent studies underscore the immune system's involvement in IDD, particularly with regards to the role of immune privileged tissues such as the nucleus pulposus (NP) becoming an immune targeting following initial disc injury.

Impact of long-term rapamycin treatment on age-related osteoarthritis in common marmoset.

Objective: Pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) can attenuate experimental osteoarthritis (OA) in young, male preclinical models. However, the potential of mTOR inhibition as a therapeutic mechanism for OA remains unknown. The goal of this study was to determine if mTOR-inhibition by oral rapamycin can modify OA pathology in the common marmoset, a translational model of age-associated OA.

Blood flow restriction training does not negatively alter the mechanical strength or histomorphology of uninjured equine superficial digital flexor tendons.

Background: Low load exercise training with blood flow restriction (BFR) has become increasingly used by human physical therapists to prescribe controlled exercise following orthopaedic injury; its effects on the equine superficial digital flexor tendon (SDFT), however, are unknown.

Objective: To investigate outcomes of pressure specific BFR walking exercise on uninjured equine SDFT biomechanics and histomorphology.

Study Design: Controlled in vivo experiment.

The common marmoset as a translational model of age-related osteoarthritis.

Age-related osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes in nearly every intra- and peri-articular tissue that contributes to disability in older adults. Studying the etiology of age-related OA in humans is difficult due to an unpredictable onset and insidious nature. A barrier in developing OA modifying therapies is the lack of translational models that replicate human joint anatomy and age-related OA progression.

Treatment with PB125 Increases Femoral Long Bone Strength in 15-Month-Old Female Hartley Guinea Pigs.

Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a transcription factor that serves as a master regulator of anti-inflammatory agents, phase I xenobiotic, and phase II antioxidant enzymes, all of which provide a cytoprotective role during disease progression. We hypothesized that oral administration of a purported phytochemical Nrf2-activator, PB125, would increase long bone strength in aging Hartley guinea pigs, a model prone to musculoskeletal decline. Male (N = 56) and female (N = 56) guinea pigs were randomly assigned to receive daily oral treatment with either PB125 or vehicle control.

TLR4 antagonism provides short-term but not long-term clinical benefit in a full-depth cartilage defect mouse model.

Purpose/aim: Cartilage injury and subsequent osteoarthritis (OA) are debilitating conditions affecting millions worldwide. As there are no cures for these ailments, novel therapies are needed to suppress disease pathogenesis. Given that joint injuries are known to produce damage-associated molecular patterns (DAMPs), our central premise is that the Toll-like receptor 4 (TLR4) pathway is a principal driver in the early response to cartilage damage and subsequent pathology.

Erythrocyte removal from bone marrow aspirate concentrate improves efficacy as intra-articular cellular therapy in a rodent osteoarthritis model.

Background: Despite the high prevalence of osteoarthritis (OA), there remains a need for additional therapeutic options. Cellular therapies with minimally manipulated cells such as bone marrow aspirate concentrates (BMAC) are increasingly popular in the U.S.

Optimization of overhead enclosure monitoring in juvenile male Dunkin Hartley guinea pigs ().

Overhead enclosure monitoring provides objective quantitative mobility measurements for animals undergoing open-field testing. Notably, protocols for testing optimization have been minimally established for the guinea pig. It is unknown whether (a) repeated exposure, (b) time-of-day, or (c) length of testing duration influence outcome parameters.

Fast, non-eccentrically loaded exercise worsens tendinopathic healing responses in a murine model.

Objective: To advance the understanding of how alterations in exercise speed and grade (flat vs 17° incline or decline) affect the quality of tendon healing, and to determine if a biomarker relationship exists between serum levels of a ColX breakdown product (CXM) and animals exposed to treadmill running protocols.

Animals: 35 male mice (C57BL/6J), 8 weeks of age.

Procedures: Mice were preconditioned on a treadmill for 14 days.

VIEW-VLU observational study of the effect of Varithena on wound healing in the treatment of venous leg ulcers.

Objective: Chronic venous hypertension, triggered by venous reflux and/or obstruction, leads to skin changes and venous leg ulcers (VLUs). Compression therapy is the standard of care, but many wounds remain unhealed. The objectives of this study were to observe the effects of endovenous chemical ablation with commercially available 1% polidocanol injectable microfoam on VLU healing and recurrence rates.

Early removal of the infrapatellar fat pad/synovium complex beneficially alters the pathogenesis of moderate stage idiopathic knee osteoarthritis in male Dunkin Hartley guinea pigs.

Background: The infrapatellar fat pad (IFP) is the largest adipose deposit in the knee; however, its contributions to the homeostasis of this organ remain undefined. To determine the influence of the IFP and its associated synovium (IFP/synovium complex or IFP/SC) on joint health, this study evaluated the progression of osteoarthritis (OA) following excision of this unit in a rodent model of naturally-occurring disease.

Methods: Male Dunkin-Hartley guinea pigs (n=18) received surgical removal of the IFP in one knee at 3 months of age; contralateral knees received sham surgery as matched internal controls.

Full and Partial Mid-substance ACL Rupture Using Mechanical Tibial Displacement in Male and Female Mice.

The anterior cruciate ligament (ACL) is the most commonly injured knee ligament. Surgical reconstruction is the gold standard treatment for ACL ruptures, but 20-50% of patients develop post-traumatic osteoarthritis (PTOA). ACL rupture is thus a well-recognized etiology of PTOA; however, little is known about the initial relationship between ligamentous injury and subsequent PTOA.

Intravenous injection of adipose-derived mesenchymal stromal cells benefits gait and inflammation in a spontaneous osteoarthritis model.

Osteoarthritis (OA) is a leading cause of morbidity among aging populations, yet symptom and/or disease-modification remains elusive. Adipose-derived mesenchymal stromal cells (adMSCs) have demonstrated immunomodulatory and anti-inflammatory properties that may alleviate clinical signs and interrupt disease onset and progression. Indeed, multiple manuscripts have evaluated intra-articular administration of adMSCs as a therapeutic; however, comparatively few evaluations of systemic delivery methods have been published.

Systemic iron reduction via an iron deficient diet decreases the severity of knee cartilage lesions in the Dunkin-Hartley guinea pig model of osteoarthritis.

Objective: Iron accumulation is emerging as a player in aging-related disorders due to its propensity for generating reactive oxygen species (ROS). Studies investigating the role of iron in the pathogenesis of primary osteoarthritis (OA) are limited. We designed a proof-of-principle study to determine the effect of systemic iron deficiency, via an iron deficient diet, on knee OA in an animal model.

Phytochemical compound PB125 attenuates skeletal muscle mitochondrial dysfunction and impaired proteostasis in a model of musculoskeletal decline.

Impaired mitochondrial function and disrupted proteostasis contribute to musculoskeletal dysfunction. However, few interventions simultaneously target these two drivers to prevent musculoskeletal decline. Nuclear factor erythroid 2-related factor 2 (Nrf2) activates a transcriptional programme promoting cytoprotection, metabolism, and proteostasis.

Nontransgenic Guinea Pig Strains Exhibit Hallmarks of Human Brain Aging and Alzheimer's Disease.

Older age is the primary risk factor for most chronic diseases, including Alzheimer's disease (AD). Current preclinical models to study brain aging and AD are mainly transgenic and harbor mutations intended to mirror brain pathologies associated with human brain aging/AD (eg, by increasing production of the amyloid precursor protein, amyloid beta [Aβ], and/or phosphorylated tau, all of which are key pathological mediators of AD). Although these models may provide insight on pathophysiological processes in AD, none completely recapitulate the disease and its strong age-dependence, and there has been limited success in translating preclinical results and treatments to humans.

Systemic administration of a pharmacologic iron chelator reduces cartilage lesion development in the Dunkin-Hartley model of primary osteoarthritis.

Iron has been emerging as a key contributor to aging-associated, chronic disorders due to the propensity for generating reactive oxygen species. To date, there are a limited number of publications exploring the role of iron in the pathogenesis of primary/age-related osteoarthritis (OA). The objective of this study was to determine whether reduced iron via pharmacologic iron chelation with deferoxamine (DFO) affected the development and/or severity of cartilage lesions in a primary OA model.

Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses.

Osteoarthritis (OA) is a common condition with diverse etiologies, affecting horses, humans, and companion animals. Importantly, OA is not a single disease, but rather a disease process initiated by different events, including acute trauma, irregular or repetitive overload of articular structures, and spontaneous development with aging. Our understanding of the pathogenesis of OA is still evolving, and OA is increasingly considered a multifactorial disease in which the innate immune system plays a key role in regulating and perpetuating low-grade inflammation, resulting in sustained cartilage injury and destruction.