This study aims to investigate the earliest alterations of bone and cartilage tissues as a result of different exercise protocols in the knee joint of Wistar rats. We hypothesize that pretraining to a continuous intense running protocol would protect the animals from cartilage degeneration. Three groups of animals were used: (i) an adaptive (pretraining) running group that ran for 8 weeks with gradually increasing velocity and time of running followed by a constant running program (6 weeks of 1.12 km/hour running per day); (ii) a non‐adaptive running (constant running) group that initially rested for 8 weeks followed by 6 weeks of constant running; and (iii) a non‐running (control) group. At weeks 8, 14, and 20 bone and cartilage were analyzed. Both running groups developed mild symptoms of cartilage irregularities, such as chondrocyte hypertrophy and cell clustering in different cartilage zones, in particular after the adaptive running protocol. As a result of physical training in the adaptive running exercise a dynamic response of bone was detected at week 8, where bone growth was enhanced. Conversely, the thickness of epiphyseal trabecular and subchondral bone (at week 14) was reduced due to the constant running in the period between 8 and 14 weeks. Finally, the intermediate differences between the two running groups disappeared after both groups had a resting period (from 14 to 20 weeks). The adaptive running group showed an increase in aggrecan gene expression and reduction of MMP2 expression after the initial 8 weeks running. Thus, the running exercise models in this study showed mild bone and cartilage/chondrocyte alterations that can be considered as early‐stage osteoarthritis. The pretraining adaptive protocol before constant intense running did not protect from mild cartilage degeneration. ... Read more

The mechanical properties of articular cartilage depend on the quality of its matrix, which consists of collagens and glycosaminoglycans (GAGs). The accumulation of advanced glycation end products (AGEs) can greatly affect the mechanics of cartilage. In the current study, we simulated the accumulation of AGEs by using L-threose to cross-link collagen molecules in the cartilage matrix (in vitro). The resulting changes in the mechanical properties (stiffness) of cartilage are then measured both at the micrometer-scale (using micro-indenter) and nanometer-scale (using indentation-type atomic force microscopy). Non-enzymatic cross-linking within the cartilage matrix was confirmed by the browning of L-threose-treated samples. We observed > 3 times increase in the micro-scale stiffness and up to 12-fold increase in the nano-scale stiffness of the glycated cartilage in the peak pertaining to the collagen fibers, which is caused by cartilage network embrittlement. At the molecular level, we found that besides the collagen component, the glycation process also influenced the GAG macromolecules. Comparing cartilage samples before and after L-threose treatment revealed that artificially induced-AGEs also decelerate in vitro degradation (likely via matrix metalloproteinases), observed at both micro- and nano-scales. The combined observations suggest that non-enzymatic glycation may play multiple roles in mechanochemical functioning of articular cartilage ... Read more

Very little is known about the structure and properties of peri-prosthetic fibrous tissue that is found around loose orthopaedic implants. We describe a method for characterizing the structural organisation (histology, confocal microscopy) as well as the nano- and micro-scale mechanical behaviour (atomic force microscopy, nanoindentation) of peri-prosthetic fibrous tissue. The tissue was collected from 11 patients undergoing revision surgery due to aseptic loosening. Sirius Red and Movat histological staining procedures indicated that the tissue mainly consists of collagen fibres and ground substance. However, large inter- and intra-patient variations in the relative proportions of these tissue components were found, as well as in collagen fibre orientation and possibly also maturation. The nano-scale Young's moduli ranged from 0-950 kPa, but showed large inter-patient variability. When the results per sample were presented in a probability density function, we could roughly discriminate one peak in the 0-100 kPa range and/or one peak in the 100-500 Pa range. These nano-scale moduli seem to respectively present the mechanical properties of glycosaminoglycan (GAG) and collagen molecules. The majority of the micro-scale Young's moduli ranged between 0.5 and 2.0 kPa for all samples. This explorative study provides new insights in (the variations of) structural organisation and mechanical properties of peri-prosthetic tissue. ... Read more