scholarly journals DEVELOPING THE COMMON MARMOSET AS A TRANSLATIONAL MODEL OF AGE-RELATED OSTEOARTHRITIS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S104-S104
Author(s):  
Dennis M Minton ◽  
Angela J Marolf ◽  
Kelly S Santangelo ◽  
Adam B Salmon ◽  
Adam R Konopka

Abstract Age is a primary risk factor for osteoarthritis (OA). The mechanisms that contribute to OA are poorly understood and disease modifying treatments have not been identified. A critical shortcoming in developing therapies is the limited number of translational models available to identify the causes of naturally occurring OA. Our goal is to use the common marmoset as a non-human primate (NHP) model of age-related OA. NHP are the closest evolutionary relative to humans and share many characteristics of human aging. The marmoset has advantages over other NHP for aging research because of their relatively short maximal lifespan and small size. Micro-computed tomography (uCT) was performed on whole-knee joints obtained from young (10 yrs, n=3) marmosets at necropsy. OA was evaluated using a clinical uCT scoring system and quantitative assessments of subchondral bone structure and ossified meniscal volume. Advancing age was positively correlated to increased uCT OA score (p<0.05, r=0.59 ), mainly through increased number and size of osteophytes and progressive subchondral bone sclerosis from the medial to both medial and lateral compartments. For marmosets displaying meniscal ossification, older marmosets had greater (p<0.05) ossified meniscal volume than middle-aged and younger marmosets, respectively. Trabecular (p=0.05) and cortical bone thickness (p<0.05) were also lower in older marmosets. These data are the first to indicate that the marmoset develops naturally occurring, age-related OA and support the pursuit of additional studies using the marmoset to identify OA mechanisms and test potential interventions.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 412-412
Author(s):  
Ricki Colman

Abstract The common marmoset (Callithrix jacchus) has been used in biomedical research for many years, but within the last decade its popularity has increased dramatically prompted to a large degree by their realized utility for neuroscience and aging research. Many factors make the marmoset an attractive model system including their genetic and physiological similarity to humans, relatively short lifespan (average of ~13 years, maximum of ~20 years), high fertility (highest of any primate, routine production of 2-3 offspring every 5-6 months), rapid development (reproductively competent by ~1.5 years of age, aged by 7-8 years of age), small size (~400 grams), human-like social structure consisting of cooperative breeding with shared parenting responsibilities, and lack of zoonotic diseases of concern to humans. Marmosets share ~93% sequence identity with the human genome and they develop similar age-related conditions as humans. Marmosets may strike the perfect balance between similarity to humans and abbreviated aging course.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S8-S9
Author(s):  
Suzette Tardif ◽  
Corinna Ross

Abstract Interest in the New World Monkey, the common marmoset, as a nonhuman primate aging model is growing. Because marmosets have a fast maturation and short life span compared with more commonly used Old World monkey models, the aging research community began to explore the potential of this model species. In addition, the relative ease with which marmosets can be bred in a barrier environment enhances their value as a life-span model. Since that time, efforts to better define what aging actually looks like in marmosets has intensified. Important findings of the past decade include: (1) a refined definition of lifespan in this species and what affects age-specific survival; (2) assessments of age-related pathological changes; (3) development of functional phenotyping relevant to aging, such as activiyy, strength, body composition, cytokine profiling; (4) support of studies using the marmoset as a preclinical model to test intervention that may modulate the aging process.


2021 ◽  
Author(s):  
Larissa K Dill ◽  
Natalie A Sims ◽  
Ali Shad ◽  
Chidozie Anyaegbu ◽  
Andrew Warnock ◽  
...  

While it is well-established that bone responds dynamically to mechanical loading, the effects of mild traumatic brain injury (mTBI) on cranial bone composition are unclear. We hypothesized that repeated mTBI (rmTBI) would change the microstructure of cranial bones, without gross skull fractures. To address this, young adult female Piebald Viral Glaxo rats received sham, 1x, 2x or 3x closed-head mTBIs delivered at 24h intervals, using a weight drop device custom built for reproducible impact. Skull bones were collected at 2 or 10 weeks after the final injury/sham procedure, imaged by micro computed tomography and analyzed at predetermined regions of interest. In the interparietal bone, proximal to the injury site, modest increases in bone thickness was observed at 2 weeks, particularly following 3x mTBI. By 10 weeks, 2x mTBI induced a robust increase in the volume and thickness of the interparietal bone, alongside a corresponding decrease in the volume of marrow cavities in the diploe region. In contrast, neither parietal nor frontal skull samples were affected by rmTBI. Our findings demonstrate time- and location-dependent effects of rmTBI on cranial bone structure, highlighting a need to consider microstructural alterations to cranial bone when assessing the consequences of rmTBI.


2019 ◽  
Vol 5 (2) ◽  
pp. 97-109 ◽  
Author(s):  
Corinna N. Ross ◽  
Adam B. Salmon

Author(s):  
Alexandra S Gersing ◽  
Pia M Jungmann ◽  
Benedikt J Schwaiger ◽  
Julia Zarnowski ◽  
Felix K Kopp ◽  
...  

ObjectivesThe primary objective of this study was to evaluate the effects of high tibial osteotomy (HTO) on subchondral bone structure assessed with MR-based trabecular bone imaging and the correlations of these effects with functional outcome and clinical symptoms.MethodsPatients with varus malalignment (6.2°±2.2°) and without a history of knee surgery (n=22; 3 women; 48.7±10.3 years) were included into this prospective study. 1.5T MRI was performed before and on average 1.5 years after HTO (amount of correction 4.7°±2.5°) and histomorphometric parameters of the trabecular bone were calculated for the medial/lateral tibia and femur. Functional outcome was assessed with validated scores focusing on sports activity including the Lysholm Score, Tegner Activity Scale and the adapted Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score.ResultsApparent trabecular number significantly decreased in all compartments of the tibiofemoral joint when comparing values before and on average 1.5 years after HTO (p<0.05 for all). Decrease in apparent trabecular number was significantly higher within the medial tibia compared with the lateral compartment (mean difference −0.24 mm−1 (95% CI −0.33 to −0.14 mm−1); p<0.001). Apparent trabecular bone thickness significantly increased within 1.5 years after HTO in the lateral femur (p=0.002) and tibia (p<0.001). The Lysholm Score and Tegner Scale demonstrated an improvement of functional outcome, and the adapted WOMAC demonstrated an improvement of pain, stiffness and physical function within 1.5 years after HTO (p<0.01), with the improvement of WOMAC correlating significantly with changes in trabecular bone thickness within the medial tibia (r=−0.48; p=0.01).ConclusionThese findings indicate a reversal of the previous subchondral bone alterations in patients with varus malalignment after undergoing HTO, while pronounced subchondral changes were associated with a better functional outcome.Level of evidenceIII


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Takahiko Noro ◽  
Kazuhiko Namekata ◽  
Atsuko Kimura ◽  
Yuriko Azuchi ◽  
Nanako Hashimoto ◽  
...  

Abstract The common marmoset (Callithrix jacchus) is a non-human primate that provides valuable models for neuroscience and aging research due to its anatomical similarities to humans and relatively short lifespan. This study was carried out to examine whether aged marmosets develop glaucoma, as seen in humans. We found that 11% of the aged marmosets presented with glaucoma-like characteristics; this incident rate is very similar to that in humans. Magnetic resonance imaging showed a significant volume loss in the visual cortex, and histological analyses confirmed the degeneration of the lateral geniculate nuclei and visual cortex in the affected marmosets. These marmosets did not have elevated intraocular pressure, but showed an increased oxidative stress level, low cerebrospinal fluid (CSF) pressure, and low brain-derived neurotrophic factor (BDNF) and TrkB expression in the retina, optic nerve head and CSF. Our findings suggest that marmosets have potential to provide useful information for the research of eye and the visual system.


2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Chen-Chen Ji ◽  
Bo Liu ◽  
Yi-Jie Shao ◽  
Ting Liang ◽  
Hua-Ye Jiang ◽  
...  

Abstract Objectives: In the treatment of osteoarthritis (OA), tramadol, a common weak opioid, has become popular due to its effectiveness in inhibition of pain. In the present study, we aimed to explore the effect of tramadol on subchondral bone, especially changes in the microstructure and mechanical properties. Methods: A mouse model of OA was established in the present study by destabilization of the medial meniscus (DMM). A vehicle or drug was administered for 4 weeks. Specimens were harvested and analyzed radiologically and histologically using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), atomic force microscopy (AFM) and histological staining to evaluate the knee joints of mice undergoing different forms of intervention. Results: In the early stages of OA induced by DMM, the subchondral bone volume fraction in the OA group was significantly higher than in the sham+vehicle (sham+veh) group, while the volume in the treatment groups was lower than in the DMM+vehicle (DMM+veh) and sham+veh groups. In addition, the elastic moduli in the treatment groups clearly decreased compared with the DMM+veh and sham+veh groups. Observations of the subchondral bone surface by SEM indicated serious destruction, principally manifesting as a decrease in lacunae and more numerous and scattered cracks. Histological staining demonstrated that there was no difference in the degeneration of either the articular cartilage or synovial cells whether tramadol was used or not. Conclusion: Although tramadol is effective in inhibiting pain in early OA, it negatively regulates the microstructure and mechanical properties of subchondral bone in joints.


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