Patellar Enthesis Research Articles

MIRNA-LADEN MAGNETIC-RESPONSIVE BIOINK FOR TENDON AND ENTHESIS TISSUE ENGINEERING

Tendons and tendon-to-bone entheses don't usually regenerate after injury, and the hierarchical organization of such tissues makes them challenging sites of study for tissue engineers. In this study, we have tried a novel approach using miRNA and a bioactive bioink to stimulate the regeneration of the enthesis. microRNAs (miRNAs) are short, non-coding sequences of RNA that act as post-transcriptional regulators of gene and protein expression [1]. Mimics or inhibitors of specific miRNAs can be used to restore lost functions at the cell level or improve healing at the tissue level [2,3]. We characterized the healing of a rat patellar enthesis and found that miRNA-16-5p was upregulated in the fibrotic portion of the injured tissue 10 days after the injury. Based on the reported interactions of miRNA-16-5p with the TGF-β pathway via targeting of SMAD3, we aimed to explore the effects of miRNA-16-5p mimics on the tenogenic differentiation of adipose-derived stem cells (ASCs) encapsulated in a bioactive bioink [4,5]. Bioinks with different properties are used for the 3D printing of biomimetic constructs. By integrating cells, materials, and bioactive molecules it is possible to tailor the regenerative capacity of the ink to meet the particular requirements of the tissue to engineer [5]. Here we have encapsulated ASCs in a gelatin-methacryloyl (GelMa) bioink that incorporates miR-16-5p mimics and magnetically responsive microfibers (MRFs). When the bioink is crosslinked in the presence of a magnetic field, the MRFs align unidirectionally to create an anisotropic construct with the ability to promote the tenogenic differentiation of the encapsulated ASCs. Additionally, the obtained GelMA hydrogels retained the encapsulated miRNA probes, which permitted the effective 3D transfection of the ASC and therefore, the regulation of gene expression, allowing to investigate the effects of the miR-16-5p mimics on the tenogenic differentiation of the ASCs in a biomimetic scenario.

MiRNAs as Potential Regulators of Enthesis Healing: Findings in a Rodent Injury Model.

MicroRNAs (miRNAs) are short non-coding RNA sequences with the ability to inhibit the expression of a target mRNA at the post-transcriptional level, acting as modulators of both the degenerative and regenerative processes. Therefore, these molecules constitute a potential source of novel therapeutic tools. In this study, we investigated the miRNA expression profile that presented in enthesis tissue upon injury. For this, a rodent enthesis injury model was developed by creating a defect at a rat's patellar enthesis. Following injury, explants were collected on days 1 (n = 10) and 10 (n = 10). Contra lateral samples (n = 10) were harvested to be used for normalization. The expression of miRNAs was investigated using a "Fibrosis" pathway-focused miScript qPCR array. Later, target prediction for the aberrantly expressed miRNAs was performed by means of the Ingenuity Pathway Analysis, and the expression of mRNA targets relevant for enthesis healing was confirmed using qPCRs. Additionally, the protein expression levels of collagens I, II, III, and X were investigated using Western blotting. The mRNA expression pattern of EGR1, COL2A1, RUNX2, SMAD1, and SMAD3 in the injured samples indicated their possible regulation by their respective targeting miRNA, which included miR-16, -17, -100, -124, -133a, -155 and -182. Furthermore, the protein levels of collagens I and II were reduced directly after the injury (i.e., day 1) and increased 10 days post-injury, while collagens III and X showed the opposite pattern of expression.

Ultrasonographic evaluation of Achilles tendon and patellar enthesis in football and basketball players: could it be useful to predict muscular and tendon injuries?

article: Ultrasonographic evaluation of Achilles tendon and patellar enthesis in football and basketball players: could it be useful to predict muscular and tendon injuries? - Medicina dello Sport 2022 September;75(3):436-45 - Minerva Medica - Journals

Enthesis: not the same in each localisation - a molecular, histological and biomechanical study.

The interphase between tendon and bone consists of a highly specialised tissue called enthesis. Typically, the enthesis is described as a succession of four different zones: tendon, non-mineralised fibrocartilage, mineralised fibrocartilage and bone. However, the microstructure of the entheses, cellular composition and mechanical properties vary depending on their anatomical location. The present study aimed to characterise three of the most relevant sites of enthesis injury in a rat model: the patellar tendon, the Achilles tendon and the supraspinatus enthesis, in terms of biomechanics, histology and genetic expression. The patellar enthesis presented the highest ultimate load and lowest stiffness of the three, while the supraspinatus was the weakest and stiffest. The histological characterisation revealed key differences at the insertion site for each enthesis. The patellar enthesis showed a large cartilaginous area at the tendon-to-bone interphase whilst this interphase was smaller in the supraspinatus entheses samples. Furthermore, the Achilles tendon enthesis displayed a more abrupt transition from tendon to bone. Additionally, each enthesis exhibited a particular and distinct pattern of expression of tenogenic, chondrogenic and osteogenic markers. This study provided valuable insights for a better understanding of the three entheses at relevant anatomical sites. Moreover, the larger cross-sectional area of the patellar enthesis, the strong mechanical properties and the easier surgical access to this location led to the conclusion that the patellar tendon enthesis site could be most suitable for the development of a preclinical model for general enthesis regeneration studies in rats.

Histopathological changes in patellar tendon enthesis of rabbit induced by electrical stimulation intensity

BackgroundEnthesis injury is a common problem in athletes and workers, which is considered closely related to overuse. However, the early pathophysiologic changes of osteotendinous junction are not well understood, and moreover, few studies investigated the relationship between intensity and pathological changes. The purpose of this study was to evaluate microstructural changes induced by different loading intensities and to find out the threshold intensity. MethodsForty-eight New Zealand White rabbits were randomly divided into six groups. One control group, the others were electrically stimulated to contract repetitively for 2 h per day, three days a week. 30% of peak tetanic force (7.06 N) was adopted to stimulate the rabbits in the 100% cyclic loading group. Other groups were stimulated with 20%, 40%, 60% and 80% of this force. After four weeks, prepared samples were stained with hematoxylin and eosin. ResultsAfter 4 weeks of cyclic loading, the shape and the distribution of tendon cells in patellar enthesis changed, the arrangement of collagen fibers became disordered and the tidemark had become irregular or even disappeared. Different stimulus intensity caused a significant change of cell density in different groups (F = 10.19, P < 0.001). The cell densities of tendon were 34.3 ± 7.9 cells/100 μm2 (L60), 38.2 ± 5.9 cells/100 μm2 (L80), 43.8 ± 10.3 cells/100 μm2 (L100) respectively, which had significant difference with CON group 22.5 ± 3.5 cells/100 μm2. The thickness of fibrocartilage zone had no significant difference among the groups. ConclusionsThe changes of histomorphology with the increasing exercise intensity elucidated that the degree of enthesis microdamage was directly related to the intensity of exercises. The findings demonstrated that 18% (used in L60 group) of peak tetanic force was the threshold intensity which could induce pathological changes in enthesis in four weeks.

Patellar tendon enthesis abnormalities and their association with knee pain and structural abnormalities in older adults

Purpose: The patellar tendon works together with the quadriceps tendon to enable knee flexion. Its attachment site (enthesis) is at risk of micro damage and degeneration. Recent studies suggest that enthesis abnormalities are associated with development of osteoarthritis through the synovio-entheseal complex. However, no studies have assessed the presence of patellar enthesis abnormalities in older adults and its association with osteoarthritis outcomes. Therefore, we aimed to describe associations between presence of patellar tendon enthesis (PTE) abnormalities visible on magnetic resonance (MR) images at baseline and knee pain, physical function limitations, and osteoarthritic structural abnormalities both cross-sectionally and longitudinally over 10.7 years. Methods: Patellar tendon enthesis abnormalities, defined as presence of abnormal bone signal and/or bone erosion were measured on T2-weighted fat suppressed fast spin echo MR images at baseline in 961 community-dwelling older adults. Knee pain and physical function limitation score were assessed using WOMAC at baseline and 10.7 years. Tibial, femoral, and patella bone marrow lesions (BMLs), cartilage volume and cartilage defects were assessed at baseline and 10.7 years, tibial bone area at baseline and 2.7 years, and infrapatellar fat pad area at baseline using validated methods. Associations were assessed using hurdle, log binomial, linear, and mixed models, after adjusting for confounders. Results: 20% of participants had bone signal and/or erosion at PTE. Cross-sectionally, presence of PTE abnormalities were associated with greater intensity of pain while going up and down stairs (β = 0.22 (95% CI; 0.03, 0.41)), greater risk of having a femoral (RR = 1.46 (1.22, 1.90)) BML, greater lateral tibial bone area (β = 25.95 (1.00, 50.91)), smaller infrapatellar fat pad area (β = −0.26 (−0.46, −0.05)), and a worse tibial cartilage defect score (RR = 1.70 (1.16, 2.47), after adjustment for age, sex, BMI, and structural confounders. Longitudinally, presence of PTE abnormalities at baseline predicted an increased risk of deleterious changes in tibial BML size (RR = 1.52 (1.12, 2.05)) only over 10.7 years but not pain or other structural changes. Conclusions: Patellar tendon enthesis abnormalities are common in the elderly. The presence of cross-sectional but not longitudinal associations suggests they commonly co-exist with other knee structural abnormalities. This suggests they may not be a major player in symptom development or structural changes with the exception of tibial BMLs.

Effects of Time to Start Training After Acute Patellar Tendon Enthesis Injuries on Healing of the Injury in a Rabbit Model

Background: A patellar tendon injury is a common injury in sports. The optimal time to start training after an acute, proximal patellar enthesis injury is still unclear. Hypothesis: The time to start training after an acute, proximal patellar enthesis injury significantly affects healing of the patellar tendon 4 weeks after the injury. Study Design: Controlled laboratory study. Methods: The left hindlimbs of 35 mature female rabbits were randomly assigned to 5 injury groups including a 4-week natural healing group (NH4W) and 4 training groups that started low-intensity training at 24 hours (POST24), 48 hours (POST48), 72 hours (POST72), and 96 hours (POST96) after an acute patellar tendon injury, with 7 limbs in each group. The right hindlimbs of the NH4W group were used as a control group (CON). An acute, proximal patellar enthesis injury was created in all injury groups. The training groups underwent low-intensity quadriceps training for 2 hours per day and 3 days per week for 4 weeks. Histological and radiographic data were collected and analyzed. Results: The cell densities of the training groups were significantly lower than those of the NH4W and CON groups (P = .01). The fibrocartilage zone was significantly thicker in the POST24, POST48, and POST72 groups compared with the CON and NH4W groups and was the thickest in the POST24 group (P = .01). The bone surface to bone volume ratio was significantly higher in all the injury groups compared with the CON group and in the POST24 group compared with the other groups (P = .01). Trabecular thickness was significantly lower in all the injury groups compared with the CON group and in the POST24 group compared with the other groups (P = .01). Conclusion: Resting without training in the first 96 hours after an acute patellar tendon enthesis injury resulted in the best recovery of cell density in the tendon enthesis 4 weeks after the injury. Starting training 96 hours after the injury resulted in the best recovery of fibrocartilage zone thickness. Starting training 48 to 96 hours after the injury resulted in the best healing of the bone component of the attachment site 4 weeks after the injury. The optimal time to start training may be longer than 96 hours after an acute patellar tendon enthesis injury for the best overall healing of the tendon enthesis 4 weeks after the injury. Clinical Relevance: A rest of a minimal 72 hours may be needed for the best healing of a patellar tendon enthesis after an acute injury. Future studies are needed to determine the optimal time to start training after an acute patellar tendon injury.

Subclinical enthesopathy in patients with psoriasis and its association with other disease parameters: a power Doppler ultrasonographic study.

This study aimed to determine the prevalence of subclinical enthesopathy in patients with psoriasis using power Doppler ultrasonography (PDUS) and its association with other disease parameters. A total of 50 patients with psoriasis (31 females) aged 19-70 years underwent a thorough clinical examination that included assessment of body mass index (BMI) and psoriasis area and severity index (PASI) score. Measurements of inflammatory markers, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum uric acid, and plain radiography of the heels, knees, and sacroiliac joints were performed for all patients. Patients without clinical evidence of arthritis or enthesitis underwent an ultrasonographic (US) examination. According to the US examination, patients were classified into group I (patients with enthesitis) and group II (patients without enthesitis). In group I, Achilles enthesis was the most common site of US enthesitis (33.3%), followed by distal patellar enthesis (22.2%), proximal patellar enthesis (16.7%), quadriceps enthesis (16.7%), and plantar aponeurosis enthesis (11.1%). There was a statistically significant positive correlation between the occurrence of enthesitis and the patient's age, disease duration, PASI score, BMI, and hyperuricemia (p<0.05 for each). In contrast, there was no significant correlation between enthesitis and sex or radiographic sacroiliitis (p>0.05 for each). In addition to the importance of PDUS as a complimentary tool for examining enthesis in patients with psoriasis, the presence of high PASI score, increased BMI and hyperuricemia, and a long disease duration can be considered as predictive parameters for the presence of psoriatic enthesitis.

THU0339 Power doppler ultrasonograpic findings in healthy pediatric enthesises

BackgroundIn Rheumatic Ultrasonographic evaluation interest has been raised about the use of power Doppler ultrasonography (PDUS) in the assessment of inflammatory changes in the articular and periarticular structures of children.Nevertheless,...