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Degeneration of articular cartilage is often triggered by a small tissue crack. As cartilage structure and composition change with age, the mechanics of cracked cartilage may depend on the tissue age, but this relationship is poorly understood. Here, we investigated cartilage mechanics and crack deformation in immature and mature cartilage exposed to a full‐thickness tissue crack using indentation testing and histology, respectively. When a cut was introduced, tissue cracks opened wider in the mature cartilage compared to the immature cartilage. However, the opposite occurred upon mechanical indentation over the cracked region. Functionally, the immature‐cracked cartilages stress‐relaxed faster, experienced increased tissue strain, and had reduced instantaneous stiffness, compared to the mature‐cracked cartilages. Taken together, mature cartilage appears to withstand surface cracks and maintains its mechanical properties better than immature cartilage and these superior properties can be explained by the structure of their collagen fibrous network.

difficulty in transfecting siRNAs in vivo. Recently, chemically modulated siRNAs which do not require transfection agents or other additional techniques such as electroporation in transfecting into cells have been developed. These siRNAs can be applied simply to cells with low cellular toxicity, and is likely to be suitable for in vivo use. Previous studies have demonstrated that the effects of intra-articular injection of ADAMTS5 or MMP13 siRNA into the knee on the delay and attenuation of articular cartilage degeneration. However, the effect of the combined siRNA injection of these two proteases is not clear. Therefore, purpose of this sturdy is to examine the effect of administration of chemically modulated MMP13 siRNA alone or in combination with ADAMTS5 siRNA in a mice OA model. Methods: OA pathology was surgically induced to C57BL/6 mice by destabilization of the medial meniscus (DMM) method, by transecting the medial meniscotibial ligament under general anesthesia. Three different siRNA injections against the DMM model were evaluated. MMP13 siRNA group was injected chemically modulated MMP13 siRNA one week after DMM surgery. Combined siRNA group was injected ADAMTS5 siRNA three days after the surgery and MMP13 siRNA four days later. Control siRNA group was injected non targeting siRNA which does not target to any gene. Histological assessment of articular cartilage at 8 weeks post DMM surgery was conducted to assess the effect of siRNA injections in osteoarthritis progression, according to the OARSI recommendation for OA knee scoring in mice. Results: Fibrillation and loss of Safranin O staining of the cartilage surface were observed in control siRNA group. Improvement was observed in the histological score in both treated group compared to the control siRNA injected group. Especially in combined siRNA group, the score was lower than MMP13 siRNA group. Conclusions: Combined treatment with MMP13 siRNA and ADAMTS5 siRNA intra-articular injection can be expected to inhibit cartilage degradation at the early phase of OA development compared to treatment MMP13 siRNA alone.