22/01/2024
Sự thoái hóa của gân
Tendon structure in health and disease 🦶
💡 Summary based on Scott (2015, https://pubmed.ncbi.nlm.nih.gov/26390273/)
👉 The classic description of the tensile load-bearing region of tendon includes 3 main components:
1️⃣ type I collagen fibers (70–80% of the dry weight of the tendon and represents almost 95% of the total collagen. Other collagens include collagen types II, III, IV, V, VI, IX, X, XII, and XIV) longitudinally oriented;
2️⃣ a well-hydrated, noncollagenous extracellular matrix (rich in glycosaminoglycans); and
3️⃣ cells. The predominant cell population in healthy tendon is traditionally categorized as collagen-producing fibroblasts, responsible for the synthesis of the collagen fibers and extracellular matrix. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2505234/ https://pubmed.ncbi.nlm.nih.gov/26390273/)
👉 Prominent features of chronic tendinopathy histopathology (FIGURE 1) include the following:
▶︎ a disorganization of collagen fibers,
▶︎ an increase in the number of vessels and sensory nerves, https://pubmed.ncbi.nlm.nih.gov/17604979/, https://pubmed.ncbi.nlm.nih.gov/23609815/, https://pubmed.ncbi.nlm.nih.gov/15958764/
▶︎ an increase in the hydrated components of the extracellular matrix, https://research.monash.edu/en/publications/human-tendon-overuse-pathology-histopathologic-and-biochemical-fi
▶︎ a breakdown of tissue (tendon/endotendon/paratendon) organization, (https://search.worldcat.org/de/title/human-tendons-anatomy-physiology-and-pathology/oclc/35103208) and
▶︎ haphazardly arranged proliferation of smaller, type III collagen fibers. (https://pubmed.ncbi.nlm.nih.gov/24571576/, https://pubmed.ncbi.nlm.nih.gov/12867575/)
👉There are frequently areas of cell death (eg, hypocellularity, https://pubmed.ncbi.nlm.nih.gov/16567784/) or, alternatively, of fibroblast reaction (eg, hypercellularity with rounded tenocytes and adhesions, https://pubmed.ncbi.nlm.nih.gov/3071152/).
📌 Indeed, it is typical to find both degenerative and reactive changes within the same biopsy, even in very severe, long-standing cases. It is also postulated that there is a resident population of fibroblast-like cells within tendons that, after injury, can differentiate into several lineages (osteoblast, chondrocyte, adipocyte, tenocyte), leading to metaplasia (eg, bony, cartilaginous, or adipocyte transformation, https://pubmed.ncbi.nlm.nih.gov/12837285/). Metaplasia is not usually discernible on imaging, unless the ossification is advanced, but is frequently encountered in biopsy specimens (reviewed in Lui, https://pubmed.ncbi.nlm.nih.gov/23671126/).
👉 The implication is that patients with chronic symptoms and evidence of structural change on imaging typically have profound underlying abnormalities that will not be quickly resolved, and that are associated with the loss of tendon function.
✅ At the cellular level, several authors have reported increased numbers of leukocytes (especially macrophages and mast cells) in chronically painful tendons (rotator cuff, patellar and Achilles tendons, https://pubmed.ncbi.nlm.nih.gov/24096896/, https://pubmed.ncbi.nlm.nih.gov/25081311/, https://pubmed.ncbi.nlm.nih.gov/20595553/, https://pubmed.ncbi.nlm.nih.gov/15958764/) as well as increased numbers of vascular cells (endothelial and smooth muscle, https://pubmed.ncbi.nlm.nih.gov/18067512/).
🔥 However, compared to the more immune-driven pathologies, such as rheumatoid arthritis, with measurable systemic inflammation, the number of leukocytes is small. In other words, there is indeed an inflammatory reaction within chronically painful tendinopathy, but to a lesser extent than that of immune-driven rheumatological disorders.
✅ Macrophages with accumulations of hemosiderin in their cytoplasm are more prevalent in tendinopathic than in normal tendon (https://pubmed.ncbi.nlm.nih.gov/9174456/); hemosiderin is an indicator of prior injury that resulted in an activation of the innate immune response. At a biochemical level, the cells in painful tendons produce increased levels of glycosaminoglycan and inflammatory mediators such as substance P and prostaglandin E2 (PGE2, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714045/, https://pubmed.ncbi.nlm.nih.gov/24563019/, https://pubmed.ncbi.nlm.nih.gov/12072760/, https://pubmed.ncbi.nlm.nih.gov/9820287/).
✅ Substance P is released by peripheral sensory nerves (https://pubmed.ncbi.nlm.nih.gov/21678472/) and repetitively stretched tendon fibroblasts (https://pubmed.ncbi.nlm.nih.gov/21625050/, https://pubmed.ncbi.nlm.nih.gov/22069500/), and activates local mast cells that may contribute to pain and fibrosis (https://pubmed.ncbi.nlm.nih.gov/22343473/). Tendon cells derived from tendinopathic tendon produce more PGE2 than cells from healthy individuals, indicating a chronic upregulation (https://pubmed.ncbi.nlm.nih.gov/12072760/).
📣 Taken together, the evidence suggests that during the rehabilitation process, any worsening of edema, morning stiffness, or delayed-onset pain should be closely monitored and controlled, as inflammation could drive the tendon further down the pathological path. An early return to sport before adequate tendon load-bearing capacity is a significant risk factor for recurrence of Achilles tendinopathy (https://pubmed.ncbi.nlm.nih.gov/23770660/).
📷 Illustration:
Pereira, H. et al. (2023). Foot and Ankle Tendinopathies. In: Longo, U.G., Denaro, V. (eds) Textbook of Musculoskeletal Disorders. Springer, Cham. https://doi.org/10.1007/978-3-031-20987-1_59
https://link.springer.com/chapter/10.1007/978-3-031-20987-1_59
