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Biology subjects

Focht, M. D. K.

Publications and source records attributed to Focht, M. D. K..

2 recordsLinked to original sources

The effect of microstructural variations in tendon and ligament on diffusion tensor MRI

The fibrous microstructure of tendons and ligaments is an important determinant of their mechanical behavior and integrity. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that enables the inference of microstructural features within fibrous tissues and has recently been used to characterize the microstructure of dense connective tissues such as tendon and ligament. However, the effect of microstructural variations in tendon and ligament on DTI metrics remains unclear. To address this gap, we simulated diffusion MRI of second harmonic generation (SHG) image-informed square lattice fiber networks to determine which microstructural features have the strongest influence on DTI metrics. Then, we performed a second set of diffusion MRI simulations for randomly dispersed fibers within synthetic tendon volumes to relate DTI metrics to the influential microstructural features, including fiber dispersion. All DTI metrics were insensitive to collagen fiber crimp. Fiber dispersion did not affect mean diffusivity, decreased axial diffusivity, increased radial diffusivity, and decreased fractional anisotropy. These results provide valuable insight into the relationships between DTI metrics and microstructural properties of tendon and ligament, which is particularly relevant for inferring microstructural changes in impaired tissue using DTI. Furthermore, our findings are an important step in the translation of DTI for clinical and computational studies of dense connective tissues such as tendon and ligament.

bioengineering↗

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

PurposeGenetic deletion of mTOR has protected against post-traumatic osteoarthritis (OA) in male mice, however, effects of pharmacological mTOR-inhibition are equivocal and have not been tested in aging models nor in female subjects. Therefore, the goal of this study was to determine if mTOR-inhibition by rapamycin can modify OA pathology in aging non-human primates and female mice. MethodsCommon marmosets were administered oral rapamycin (1mg/kg/day) or vehicle starting near mid-life until death. Five-month-old, female C57BL/6J mice were treated with vehicle or rapamycin (IP, 2mg/kg, 3x/week) for 8-weeks following non-invasive ACL rupture. Knee OA pathology was assessed via microCT and histology. Phosphorylation of mTORC1 (p-RPS6S235/36) and mTORC2 (p-AktS473, p-NDRG1T638, p-PKCT348) substrates were evaluated via western blot in articular cartilage, meniscus, and/or infrapatellar fat pad. ATDC5 cells were cultured with rapamycin to determine time and dose effects on mTORC1/2 signaling. ResultsIn marmosets, rapamycin did not impact age-related radiographic OA severity or cartilage pathology but increased medial meniscus calcification and lowered lateral tibia subchondral thickness, particularly in females. In female mice, rapamycin worsened ACLR-induced meniscus calcification and cartilage pathology. In marmoset and mouse joint tissues, rapamycin inhibited mTORC1 and increased p-AktS473 but not p-NDRG1T638 or p-PKCT348. This mTOR signaling pattern was replicated in ATDC5 cells during exposure to low concentrations of rapamycin. ConclusionsRapamycin attenuated mTORC1 signaling with feedback activation of AktS473 in articular cartilage, meniscus, and/or infrapatellar fat pad and was accompanied by deleterious effects on meniscus calcification and/or cartilage pathology in female mice and common marmosets.

physiology↗