Background: Osteoarthritis (OA) is a whole joint disease that affects all joint tissues, with changes in the articular cartilage (AC), subchondral bone and synovium. Pathologies in menisci and ligaments, however, are rarely analysed, although both are known to play vital roles in the mechanical stability of the joint. The aim of our study was to describe the pathological changes in menisci and ligament during disease development in murine spontaneous and post-traumatic surgically induced OA and to quantify tissue mineralisation in the joint space using microcomputed tomography (μCT) imaging during OA progression. Methods: Knees of Str/ort mice (spontaneous OA model; 26-40 weeks) and C57CBA F1 mice following destabilisation of medial meniscus (DMM) surgery (post-traumatic OA model; 8 weeks after DMM), were used to assess histological meniscal and ligament pathologies. Joint space mineralised tissue volume was quantified by μCT. Results: Meniscal pathological changes in Str/ort mouse knees were associated with articular cartilage lesion severity. These meniscal changes included ossification, hyperplasia, cell hypertrophy, collagen type II deposition and Sox9 expression in the fibrous region near the attachment to the knee joint capsule. Anterior cruciate ligaments exhibited extracellular matrix changes and chondrogenesis particularly at the tibial attachment site, and ossification was seen in collateral ligaments. Similar changes were confirmed in the post-traumatic DMM model. μCT analysis showed increased joint space mineralised tissue volume with OA progression in both the post-traumatic and spontaneous OA models. Conclusions: Modifications in meniscal and ligament mineralisation and chondrogenesis are seen with overt AC degeneration in murine OA. Although the aetiology and the consequences of such changes remain unknown, they will influence stability and load transmission of the joint and may therefore contribute to OA progression. In addition, these changes may have important roles in movement restriction and pain, which represent major human clinical symptoms of OA. Description of such soft tissue changes, in addition to AC degradation, should be an important aspect of future studies in mouse models in order to furnish a more complete understanding of OA pathogenesis.

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Tendon transcriptomics is a rapidly growing field in musculoskeletal biology. The ultimate aim of many current tendon transcriptomic studies is characterization of in vitro, ex vivo, or in vivo, healthy, and diseased tendon microenvironments to identify the underlying pathways driving human tendon pathology. The transcriptome interfaces between genomic, proteomic, and metabolomic signatures of the tendon cellular niche and the response of this niche to stimuli. Some of the greatest bottlenecks in tendon transcriptomics relate to the availability and quality of human tendon tissue, hence animal tissues are frequently used even though human tissue is most translationally relevant. Here, we review the variability associated with human donor and procurement factors, such as whether the tendon is cadaveric or a clinical remnant, and how these variables affect the quality and relevance of the transcriptomes obtained. Moreover, age, sex, and health demographic variables impact the human tendon transcriptome. Tendons present tissue‐specific challenges for cell, nuclei, and RNA extraction that include a dense extracellular matrix, low cellularity, and therefore low RNA yield of variable quality. Consideration of these factors is particularly important for single‐cell and single‐nuclei resolution transcriptomics due to the necessity for unbiased and representative cell or nuclei populations. Different cell, nuclei, and RNA extraction methods, library preparation, and quality control methods are used by the tendon research community and attention should be paid to these when designing and reporting studies. We discuss the different components and challenges of human tendon transcriptomics, and propose pipelines, quality control, and reporting guidelines for future work in the field.