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Orthopedic and Rehabilitation Engineering

Orthopedic and Rehabilitation Engineering - Poster Session E

Poster AA5 - Medial cartilage defect drives matrix and cell pathology in compartment-matched meniscus

Saturday, October 26, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Initiating injury to soft tissues of the joint leads to osteoarthritis (OA) development but little is known about joint tissue crosstalk and how an initiating injury to cartilage drives joint deterioration as a whole. There is clinical evidence that untreated cartilage defects lead to meniscus degeneration [Jungmann+2014], but it is unknown how unilateral cartilage defects affect the menisci in the medial and lateral joint compartments. Clinically, it is well established that the structure and organization of the extracellular matrix (ECM) of the meniscus is changed in OA [Battistelli+2019]. Specifically, meniscal hypertrophy, characterized by rounded cells and increased deposition of proteoglycans, is a consequence of OA progression [Karjalainen+2021]. However, to our knowledge, no studies in preclinical models have identified structural and organizational changes in the meniscus following a focal cartilage defect. Therefore, the objective of this study was to examine the changes of proteoglycan content and how this compositional change affects cell morphology in menisci adjacent to cartilage defects compared to healthy controls. We hypothesize that following a cartilage defect, proteoglycan content will increase in underlying meniscus tissue, which will subsequently cause changes in cell morphology.

Materials and

Methods:  Medial and lateral menisci were harvested from an in vivo osteochondral defect model in New Zealand white male rabbits, which are well-characterized and widely used to study articular cartilage repair [Meng+2020]. Animal studies were performed in accordance with approval from the New York University Institutional Animal Care and Use Committee (IACUC: 2017-0025). Rabbits underwent surgery to create osteochondral defects on the medial condyle (Fig. 1), were injected with saline at 4 weeks, and were sacrificed 12 weeks post-surgery. Four groups of menisci were studied: (1) medial defect (in contact with defected condyle), (2) lateral defect (adjacent compartment to defected condyle), (3) medial no defect (control), and (4) lateral no defect (control). The osteochondral defect model positions the medial meniscus to be in contact with the injured cartilage whereas the lateral meniscus remains in contact with the uninjured condyle. Meniscus (control n=4, defect n=2) tissues were fixed in 10% formalin buffered solution, switched to 70% ethanol, embedded in paraffin wax, and sectioned for histological processing. Histological slides were stained with Safranin-O followed by imaging under brightfield. Percentage of GAG area covered in the menisci and assessment of roundness were performed using ImageJ. Roundness was analyzed by averaging results from 7-10 400x micrographs per meniscus. The effects of the defect on the percentage of GAG area were analyzed using a 1-way ANOVA with Tukey’s multiple comparisons test (* = p < 0.05). Pearson correlation coefficients were computed to assess the linear relationship between roundness and GAG coverage in the meniscus.

Results, Conclusions, and Discussions: The medial menisci of defect joints (n=2) show increased GAG composition compared to controls (n=4), as indicated by the red in the Safranin-O micrographs (Fig. 2A-D). This is consistent with other studies showing that late-stage OA menisci or menisci with traumatic tears displayed increases in proteoglycan deposition [Yoshioka+2022]. Quantification of GAG content showed a 5.7 fold increase in Safranin-O staining in medial defect joint menisci but no difference between lateral menisci (Fig. 2E). The compartmental nature of this GAG increase suggests that the defect in the medial condyle may lead to higher contact pressures and aberrant loading conditions on the compartment-matched underlying meniscus, leaving the joint vulnerable to degenerative processes. Healthy knees have a load balance between the condyle and meniscus, but when the meniscus is injured, excess load is transferred to the articular cartilage [Maher+2017]. Thus, it is reasonable to conjecture that a defect in the cartilage, as in this study, may increase abnormal compressive loading, increasing hypertrophy of the meniscal tissue, manifesting as an increase in proteoglycan production and subsequent cell rounding. While there were trending differences between the roundness (Fig. 2G) of cells in menisci with defects vs. no defect joints (p=0.063), there was a significant correlation between the local GAG area coverage and cell roundness (Fig. 2F&H). This is consistent with previous work showing that the inner region of human OA menisci had increased GAG staining via histological analysis and that increased GAG corresponded to rounded cells [Wang+2020]. These cells in GAG rich regions may undergo hypertrophic differentiation, as demonstrated by their increased roundness, which may suggest progression towards an osteoarthritic pathology [Yoshioka+2016]. This study demonstrated that a medial cartilage defect can have cascading effects by driving pathology in adjacent tissues, as demonstrated by the altered meniscal ECM and cell morphology. While the medial condylar defect affected the underlying compartment-matched menisci, the lateral menisci in joints with defects were unaffected at this time point (12 weeks post-injury). Further understanding the regulation of GAG deposition and fibrochondrocyte pathology in injured or diseased meniscus tissue could inform further therapeutics and disease progression of the tissue.

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