Increased mast cell numbers in human patellar tendinosis: correlation with symptom duration and vascular hyperplasia

Abstract

Objectives: The cellular basis of painful tendon overuse pathology (tendinosis) is poorly understood. It has been suggested that because of the close anatomical associations between mast cells and vessels in connective tissues, mast cells may mediate the development of tendon hypervascularity or oedema. Objectives: To examine the distribution of mast cells in men and women with patellar tendinopathy. Design: Case-control study. Methods: Tendinopathic tissue was collected at open debridement of the patellar tendon and a control tendon from patients undergoing intramedullary nailing of the tibia. The tendon was assessed immunohistochemically by evaluating the distribution of mast cells (AA1), and markers for T lymphocytes (CD3) and macrophages (CD68). The vessel-area fraction was quantified using computer-assisted digital image analysis. Results: The prevalence of mast cells per mm 2 (mean 3.3 (SD 3.0)) was greater in tendinosis tissue than in controls (1.1 (1.5); p = 0.036). In patients with tendinosis, mast cell density was moderately correlated with the vesselarea fraction (r 2 = 0.49) and with symptom duration (r 2 = 0.52). Conclusion: Mast-cell prevalence in patellar tendinopathy was increased and was predominantly associated with vascular hyperplasia, particularly in patients with longstanding symptoms. Future research should investigate whether mast cells play direct or indirect modulatory roles in the development and progression of human tendinosis.Repetitive overuse tendon injury (tendinopathy) is a major burden on the healthcare system and a challenge to orthopaedic and sports medicine practitioners.1 Clinical symptoms include pain, swelling, and impaired function. Despite the increased vascular flow and vascular hyperplasia that characterise tendinosis, an acute cellular inflammation (neutrophils, macrophages, lymphocytes) is rarely reported in the chronic stages. This lack of typical acute inflammatory cells has led to increasing adoption of the term ''tendinosis'' as opposed to ''tendonitis''. 4 Recently, Schubert et al 5 compared the numbers of CD68+ macrophages, CD3+ T lymphocytes, CD20+ B lymphocytes, and granulocytes in 10 patients with Achilles tendinosis and 10 patients with an acutely ruptured Achilles tendon. In this study, patients with tendinosis displayed increased numbers of macrophages and lymphocytes in association with hypervascular tissue, whereas patients with acutely ruptured tendon displayed greater numbers of granulocytes.5 Thus, inflammatory and reparative cell types may play a role in the pathogenesis of tendinosis and the development of vascular hyperplasia in chronic tendon lesions.Along with macrophages and lymphocytes, mast cell numbers are also known to be increased in a variety of chronic inflammatory or fibrotic disorders. In addition to their well known physiological role in triggering allergic reactions, mast cells release a variety of vasoactive, angiogenic and profibrotic substances that are either stored in granules or synthesised de novo in response to hypo...

Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles tendon rupture

“…This increase of MCs was particularly prominent in the MTJ but was also seen in the mid-tendon and BTJ. Previous clinical studies based on samples derived from patients suffering from AT rupture have provided limited support for an increase in MC numbers during healing (Scott et al 2008). Moreover, an increase in MC density has been suggested after rabbit deep flexor tendon repair (Berglund et al 2010) and in the tendinopathy seen in the calcaneal tendon overuse rat model (Pingel et al 2013).…”

Sodium cromolyn reduces expression of CTGF, ADAMTS1, and TIMP3 and modulates post‐injury patellar tendon morphology

“…7 This study contributes evidence that tendon repair is physiologically influenced by mast cells and their products which are known to accumulate following injury. 6 Mast cells may be involved in the initial inflammation following injury, and may also influence later events through the secretion or release of soluble factors, Figure 3. Patellar tendons were systematically examined with multiphoton (A,D,G) and second harmonic generation (B,E,H) and merged images were created (C,F,I)-all images at same magnification (63Â objective, please see Materials and Methods Section for details).…”

“…6 Mast cells, in addition to their well known role in mediating allergic reactions, also contribute to the repair and remodeling phases of soft tissue healing by releasing factors which promote proliferative and fibrogenic activity (e.g., TGFb, PDGF) as well as potent enzymes known to influence tissue repair in a variety of ways (e.g., mast cell tryptase, CPA3). A previous study reported an increased number of mast cells following acute tendon injury, 7 but to our knowledge there has not been an experimental approach to examine the implications of mast cell inhibition following tendon injury.…”

Neuropeptides in tendinopathy

“…When specific immunolabeling is performed, mast cells are found to be more prominent in tendinopathy tissue, mostly in association with microvessels (57). These mast cells express tryptase, a potent angiogenic factor (57). Mast cells are also a prominent source of nerve growth factor, which may play a role in the neural sprouting described above for acute and chronic tendon injuries (58).…”

“…When specific immunolabeling is performed, mast cells are found to be more prominent in tendinopathy tissue, mostly in association with microvessels (57). These mast cells express tryptase, a potent angiogenic factor (57).…”