01/21/2023
This gets a little science heavy but the overall message is important.
How do meniscal tears and injuries lead to knee osteoarthritis?
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👉 Patients with minor meniscus tears are 3-times more likely to develop post-traumatic osteoarthritis (PTOA) than patients with healthy menisci, and the number increases nearly 8-fold in cases of severe meniscal damage among individuals 50–79 years old. https://pubmed.ncbi.nlm.nih.gov/19248082/
👉Of patients who undergo meniscectomy, about 50% will develop PTOA within 10–20years, a relative risk 10-times greater than a healthy reference population [https://pubmed.ncbi.nlm.nih.gov/17761605/]. Likewise, a failed meniscus repair is associated with a 5-fold increased risk for PTOA development [https://pubmed.ncbi.nlm.nih.gov/33547912/].
🤔🤷♂️ However, the factors that contribute to PTOA development are still unclear.
💡 Bradley et al. (2023) therefore reviewed the underlying factors contributing to this massive increase of risk. https://pubmed.ncbi.nlm.nih.gov/36479669/. The authors documented the interplay of biological and biomechanical factors following meniscal injury (figure):
1⃣ Biomechanically, meniscus tears frequently lead to increased meniscus extrusion and altered stresses and strains in the joint. https://pubmed.ncbi.nlm.nih.gov/20516315/, https://pubmed.ncbi.nlm.nih.gov/22653191/, https://pubmed.ncbi.nlm.nih.gov/22614907/
When a meniscus is torn or injured, stress along the circumferentially oriented collagen fibers, referred to as hoop stress, is disrupted, making the meniscus more susceptible to extrusion. https://www.facebook.com/photo/?fbid=773880820585041&set=a.759955141977609, https://pubmed.ncbi.nlm.nih.gov/25296900/, https://pubmed.ncbi.nlm.nih.gov/27331081/
Meniscus extrusion may be problematic because it leaves the articular cartilage more susceptible to decreased joint congruity and higher contact stresses. https://pubmed.ncbi.nlm.nih.gov/22653191/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906039/,
For example, cadaveric studies have estimated that removal of the medial meniscus can increase contact stress between the articulating cartilage surfaces by 100% and that removal of the lateral meniscus can increase contact stress by 200–300% [https://pubmed.ncbi.nlm.nih.gov/23016106/].
2⃣ Biologically, these aberrations in mechanical loading result in the upregulation of pro-inflammatory and catabolic factors, which hinder meniscus healing. Meniscus tears often lead to an upregulation of inflammatory cytokines, such as IL-1, IL-6, and TNF-α, an increase in catabolic enzymes, such as MMPs, an increase in T cells, and potentially increases in monocytes:
➡ Within the first 24 h following an acute knee injury, concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) are increased in the synovial fluid [https://pubmed.ncbi.nlm.nih.gov/22874525/]. In patients, 3 or more months post-injury, concentrations of IL-6, IL-8, TNF-α, and IL-10 are higher in injured knees compared to normal knees, while IL-1 receptor antagonist (IL-1Ra) and IL-1β are significantly lower [https://pubmed.ncbi.nlm.nih.gov/27107410/].
➡ These inflammatory cytokines are prominent regulators of numerous catabolic enzymes, including MMPs. The collagenases MMP-1, MMP-8, MMP-13, and membrane type 1 MMP can cleave the intact triple helical collagen fibrils into one-quarter and three-quarter length fragments [https://pubmed.ncbi.nlm.nih.gov/9119997/], which are subsequently degraded by other MMPs, such as MMP-2 and MMP-9 [https://pubmed.ncbi.nlm.nih.gov/18619669/].
➡ Therefore, the upregulation in MMP activity and pro-inflammatory mediator prostaglandin E2 (PGE2) in the synovial fluid of meniscus-injured leads to an enhanced pro-inflammatory and catabolic environment that may contribute to PTOA development. https://pubmed.ncbi.nlm.nih.gov/27813662/.
➡ Likewise, meniscus injury leads to an immune cell-rich joint environment that consists largely of T cells, with multiple T-helper phenotypes [https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-021-02661-1] and monocytes. Elevation of monocytes following meniscus injury suggests that these cells may be migrating into the joint and differentiating into pro-inflammatory M1 macrophages that can release inflammatory cytokines, namely IL-1, IL-6, IL-12, and TNF-α [https://pubmed.ncbi.nlm.nih.gov/31469192/].
💡These changes broadly promote inflammation and breakdown of the extracellular matrix, which results in decreased mechanical properties of the tissue, as well as suppression of cellular proliferation and repair. The two-pronged disruption of both biomechanical and biological homeostasis leads to a positive feedback cycle, whereby each factor reinforces the degeneration spurred by the other, resulting in a sustained environment that hinders tissue repair (see figure).
