Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.

Background/Objectives: Achilles tendon injuries exhibit slow and incomplete healing due to limited vascularity, cellularity, and a complex extracellular matrix (ECM). Biologically derived ECM-based therapies have emerged as promising strategies to enhance tendon repair by providing native biochemical cues. In this study, the efficacy of injectable human tendon-derived ECM (hT-ECM) was investigated using a rat Achilles tenotomy model. Methods: Percutaneous tenotomy of the right Achilles tendon in 50 rats was performed. The animals were subjected to either no treatment as a control group (CON) or hT-ECM treatment group (ECM). Tendon healing was evaluated at 1 and 6 weeks using biomechanical, histological, transmission electron microscopy, Western blot, and immunohistochemical analysis. Results: At 6 weeks, the ECM group exhibited higher load to failure (54.5 ± 15.0 N) than the CON group (28.6 ± 13.7 N) (p < 0.05). Histological evaluation revealed progressive restoration of the injured tendon in both groups over the healing period, with comparable results observed between the groups. Ultrastructural analysis revealed that the ECM group exhibited significantly increased collagen fibrils diameters (74.1 ± 19.1 nm) than the CON group (53.8 ± 13.8 nm) (p < 0.001). Western blot exhibited that collagen I (COL I) expression at 6 weeks was significantly higher in the ECM group compared with the CON group (p < 0.05). Conclusions: These outcomes suggest that injectable hT-ECM improves early repair responses in a rat Achilles tenotomy model. Molecular analyses suggested that the therapeutic effects of hT-ECM injection could be linked to enhanced collagen type I production. Based on the study, hT-ECM injection might be a good adjuvant option for the treatment of Achilles tendon injuries.

Background: Hypermobile Ehlers–Danlos syndrome (hEDS), the most common EDS subtype, is characterized by chronic pain and joint laxity, yet no definitive causative genes or imaging-based diagnostic criteria have been established. This study investigated the genetic basis of hEDS using whole-exome sequencing (WES) and objectively evaluated ankle instability. Methods: We conducted an observational cohort study with a case–control comparison, including 22 patients and a three-generation Korean family (six individuals, four affected) diagnosed with hEDS by the 2017 criteria. WES was performed; ankle laxity was assessed by the anterior drawer test (ADT), stress ultrasonography, and stress radiography. Healthy young adults (n = 24, Beighton score < 5) from our previous study served as controls. Results: The hEDS cohort had a mean Beighton score of 8.5, with all participants reporting a family history of hypermobility and musculoskeletal complications. Family-based WES identified variants in CD44 (c.1516 + 1G > A), ITIH2 (c.783C > G), and ADAM21 (c.397C > T) in all affected individuals. In 22 unrelated patients, 114 variants in 103 candidate genes were identified; 17 patients harbored variants in genes from the same pathways as the family-derived causative genes. Compared with controls, the hEDS group showed significantly greater manual ADT grade, anterior talofibular ligament (ATFL) length at rest and under stress, dynamic ATFL change, anterior talar translation, and talar tilt. Conclusions: These findings provide molecular evidence that hEDS is a multifactorial disorder involving interconnected biological pathways, and confirm ankle instability as a clinically meaningful diagnostic feature. These complementary approaches may improve diagnostic accuracy and provide insights into the prognosis and therapeutic strategies for hEDS.