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The relationships among spatiotemporal collagen gene expression, histology, and biomechanics following full-length injury in the murine patellar tendon.

ABSTRACT: Tendon injuries are major orthopedic problems that worsen as the population ages. Type-I (Col1) and type-II (Col2) collagens play important roles in tendon midsubstance and tendon-to-bone insertion healing, respectively. Using double transgenic mice, this study aims to spatiotemporally monitor Col1 and Col2 gene expression, histology, and biomechanics up to 8 weeks following a full-length patellar tendon injury. Gene expression and histology were analyzed weekly for up to 5 weeks while mechanical properties were measured at 1, 2, 5, and 8 weeks. At week 1, the healing region displayed loose granulation tissue with little Col1 expression. Col1 expression peaked at 2 weeks, but the ECM was highly disorganized and hypercellular. By 3 weeks, Col1 expression had reduced and by 5 weeks, the ECM was generally aligned along the tendon axis. Col2 expression was not seen in the healing midsubstance or insertion at any time point. The biomechanics of the healing tissue was inadequate at all time points, achieving ultimate loads and stiffnesses of 48% and 63% of normal values by 8 weeks. Future studies will further characterize the cells within the healing midsubstance and insertion using tenogenic markers and compare these results to those of tendon cells during normal development.

SUBMITTER: Dyment NA

PROVIDER: S-EPMC3181390 | biostudies-other | 2012 Jan

REPOSITORIES: biostudies-other

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The relationships among spatiotemporal collagen gene expression, histology, and biomechanics following full-length injury in the murine patellar tendon.

Dyment Nathaniel A NA Kazemi Namdar N Aschbacher-Smith Lindsey E LE Barthelery Nicolas J NJ Kenter Keith K Gooch Cynthia C Shearn Jason T JT Wylie Christopher C Butler David L DL

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20110622 1

Tendon injuries are major orthopedic problems that worsen as the population ages. Type-I (Col1) and type-II (Col2) collagens play important roles in tendon midsubstance and tendon-to-bone insertion healing, respectively. Using double transgenic mice, this study aims to spatiotemporally monitor Col1 and Col2 gene expression, histology, and biomechanics up to 8 weeks following a full-length patellar tendon injury. Gene expression and histology were analyzed weekly for up to 5 weeks while mechanica ...[more]

PMID: 21698662

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Project description:Flexor tendinopathy is a common problem affecting humans and animals. Tendon healing is poorly understood and the outcomes of conservative and surgical management are often suboptimal. While often considered a localized injury, recent evidence indicates that in the short term, tendinopathic changes are distributed widely throughout the tendon, remote from the lesion itself. Whether these changes persist throughout healing is unknown. The aim of this study was to document gene expression, histopathological and biomechanical changes that occur throughout the superficial digital flexor tendon (SDFT) up to 16 weeks post-injury, using an ovine surgical model of tendinopathy. Partial tendon transection was associated with decreased gene expression for aggrecan, decorin, fibromodulin, tissue inhibitors of metalloproteinases (TIMPS 1, 2 and 3), collagen I and collagen II. Gene expression for collagen III, lumican and matrix metalloproteinase 13 (MMP13) increased locally around the lesion site. Expression of collagen III and MMP13 decreased with time, but compared to controls, collagen III, MMP13 and lumican expression remained regionally high throughout the study. An increase in TIMP3 was observed over time. Histologically, operated tendons had higher pathology scores than controls, especially around the injured region. A chondroid phenotype was observed with increased cellular rounding and marked proteoglycan accumulation which only partially improved with time. Biomechanically, partial tendon transection resulted in a localized decrease in elastic modulus (in compression) but only at 8 weeks postoperatively. This study improves our understanding of tendon healing, demonstrating an early 'peak' in pathology characterized by altered gene expression and notable histopathological changes. Many of these pathological changes become more localized to the region of injury during healing. Collagen III and MMP13 expression levels remained high close to the lesion throughout the study and may reflect the production of tendon tissue with suboptimal biomechanical properties. Further studies evaluating the long-term response of tendon to injury (6-12 months) are warranted to provide additional information on tendon healing and provide further understanding of the mechanisms underlying the pathology observed in this study.

Project description:Background/objectiveGraft-tunnel length mismatch is a common intraoperative technical problem for anterior cruciate ligament reconstruction (ACLR) using a bone-patellar tendon-bone graft (BPTB). The patella-to-condyle and the patella-to-notch distances are two measurements in an anteroposterior knee radiograph. The objective of this study was to evaluate the sensitivities, specificities and reliabilities of those 2 measurements for detecting patients who had a patellar tendon length exceeding 45?mm.MethodsPreoperative plain radiographs of patients who underwent ACLR with a BPTB graft were evaluated independently by two orthopaedic surgeons 3 times each at 2-weekly intervals. The sensitivities and specificities of the two measurements for detecting patients who have a patellar tendon length exceeding 45?mm were calculated. The optimal cutoff point was estimated using Youden index, and the receiver operating characteristic (ROC) curve and area under the curve (AUC) were evaluated with a 95% CI. As for the inter- and intra-rater reliabilities, intraclass correlation coefficients (ICC) were determined.ResultsOne hundred and twenty-seven patients with an average age of 29.5 years old were evaluated. The mean patellar tendon length was 41.3?±?5.0?mm. Patients with a length more than 45?mm (20 patients, 16%) had significantly higher patella-to-condyle and patella-to-notch distances, and more frequent use of bone staples for distal graft fixation than patients with a length???45?mm. To detect patients with a patellar tendon length over 45?mm, the optimal cutoff point for the patella-to-condyle distance was set at 14.5?mm, which had a sensitivity of 80%, specificity of 71%, and AUC of 0.76. In the case of the patella-to-notch distance, the cutoff point of 5.5?mm had a sensitivity of 80%, specificity of 66%, and AUC of 0.73. The intra- and inter-rater reliabilities of the two measurements were excellent, with ICCs of over 0.90.ConclusionsPreoperative measurements of the patella-to-condyle and the patella-to-notch distances in AP knee radiographs can be valuable tools, with good sensitivities and specificities, for the determination of the patellar tendon length when using a BPTB graft for an ACLR. They had an acceptable level of discrimination capability and excellent reliability.

Project description:BACKGROUND:Regular loading of tendons may counteract the negative effects of aging. However, the influence of strength training loading magnitude on tendon mechanical properties and its relation to matrix collagen content and collagen cross-linking is sparsely described in older adults. The purpose of the present study was to compare the effects of moderate or high load resistance training on tendon matrix and its mechanical properties. METHODS:Seventeen women and 19 men, age 62-70?years, were recruited and randomly allocated to 12?months of heavy load resistance training (HRT), moderate load resistance training (MRT) or control (CON). Pre- and post-intervention testing comprised isometric quadriceps strength test (IsoMVC), ultrasound based testing of in vivo patellar tendon (PT) mechanical properties, MRI-based measurement of PT cross-sectional area (CSA), PT biopsies for assessment of fibril morphology, collagen content, enzymatic cross-links, and tendon fluorescence as a measure of advanced glycation end-products (AGEs). RESULTS:Thirty three participants completed the intervention and were included in the data analysis. IsoMVC increased more after HRT (+?21%) than MRT (+?8%) and CON (+?7%) (p?<?0.05). Tendon stiffness (p?<?0.05) and Young's modulus (p?=?0.05) were also differently affected by training load with a reduction in CON and MRT but not in HRT. PT-CSA increased equally after both MRT and HRT. Collagen content, fibril morphology, enzymatic cross-links, and tendon fluorescence were unaffected by training. CONCLUSION:Despite equal improvements in tendon size after moderate and heavy load resistance training, only heavy. load training seemed to maintain tendon mechanical properties in old age. The effect of load magnitude on tendon biomechanics was unrelated to changes of major load bearing matrix components in the tendon core. The study is a sub-study of the LISA study, which was registered at http://clinicaltrials.gov (NCT02123641) April 25th 2014.

Dataset Information

The relationships among spatiotemporal collagen gene expression, histology, and biomechanics following full-length injury in the murine patellar tendon.

Publications

The relationships among spatiotemporal collagen gene expression, histology, and biomechanics following full-length injury in the murine patellar tendon.

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