Dataset Information

Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon.

ABSTRACT: This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh)/parathyroid hormone-related protein (PTHrP) signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I), Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. Ihh signal blocking group was set up using Ihh signaling pathway-specific blocking agent cyclopamine. PTHrP enhancement group was set up using PTHrP reagent. Ihh/PTHrP double intervention group, as well as control group, was included to study the regulatory mechanisms of the Ihh/PTHrP signaling pathway in fibrochondrocytes. Under low cyclic stress tensile (CTS), PTHrP, Col I, and Col II gene expression and protein synthesis increased. Under high CTS, Ihh and Col X gene expression and protein synthesis increased. Blocking Ihh signaling with cyclopamine resulted in reduced PTHrP gene expression and protein synthesis and increased Col X gene expression and protein synthesis. Ihh and PTHrP coregulate fibrochondrocyte proliferation and differentiation in entheses through negative feedback regulation. Fibrochondrocyte is affected by the CTS. This phenomenon is regulated by stress stimulation through the Ihh/PTHrP signaling pathway.

SUBMITTER: Han X

PROVIDER: S-EPMC5138489 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon.

Han Xuesong X Zhuang Yanfeng Y Zhang Zhihong Z Guo Lin L Wang Wanming W

Stem cells international 20161122

This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh)/parathyroid hormone-related protein (PTHrP) signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I), Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. Ihh ...[more]

PMID: 27994624

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Project description:BackgroundMechanical loading stimulates Achilles tendon healing. However, various degrees of loading appear to have different effects on the mechanical properties of the healing tendon, and strong loading might create microdamage in the tissue. This suggests that different mechanisms might be activated depending on the magnitude of loading. The aim of this study was to investigate these mechanisms further.MethodsFemale rats had their right Achilles tendon cut transversely and divided into three groups: 1) unloading (calf muscle paralysis by Botox injections, combined with joint fixation by a steel-orthosis), 2) mild loading (Botox only), 3) strong loading (free cage activity). Gene expression was analyzed by PCR, 5 days post-injury, and mechanical testing 8 days post-injury. The occurrence of microdamage was analyzed 3, 5, or 14 days post-injury, by measuring leakage of injected fluorescence-labelled albumin in the healing tendon tissue.ResultsPeak force, peak stress, and elastic modulus of the healing tendons gradually improved with increased loading as well as the expression of extracellular matrix genes. In contrast, only strong loading increased transverse area and affected inflammation genes. Strong loading led to higher fluorescence (as a sign of microdamage) compared to mild loading at 3 and 5 days post-injury, but not at 14 days.DiscussionOur results show that strong loading improves both the quality and quantity of the healing tendon, while mild loading only improves the quality. Strong loading also induces microdamage and alters the inflammatory response. This suggests that mild loading exert its effect via mechanotransduction mechanisms, while strong loading exert its effect both via mechanotransduction and the creation of microdamage.ConclusionIn conclusion, mild loading is enough to increase the quality of the healing tendon without inducing microdamage and alter the inflammation in the tissue. This supports the general conception that early mobilization of a ruptured tendon in patients is advantageous.

Project description:BackgroundInfection following Achilles tendon surgery is a devastating complication and can be difficult to treat and often leads to poor outcomes. A number of treatments have been described, but there is little information concerning outcomes of these treatments. Our purpose was to evaluate the clinical and functional outcomes of patients who have undergone treatment for an infected Achilles tendon after acute and chronic midsubstance repair.MethodsWe retrospectively reviewed the medical records of 20 patients who had undergone surgical treatment for an infected Achilles tendon between 2000 and 2016. The mean follow-up time was 21 months (range, 2-68 months). All patients underwent extensive debridement of the tendon with removal of all infected tissue and foreign material. Soft tissue wound coverage was utilized for large wounds that were not amenable to primary or secondary closure. All patients received culture-specific intravenous (IV) antibiotics for 3 to 6 weeks. Postoperatively, the extremity was immobilized in a splint followed by a cast until the wound was healed. The cast was then replaced with a walking boot and the patients were provided a physical therapy program. Functional outcomes were measured using the Foot and Ankle Ability Measure (FAAM) Activity of Daily Living (ADL) scale.ResultsAll wounds had healed at the time of last follow-up. Three patients (15%) required an unplanned return to the operating room for repeat debridement. All patients were able to walk without the use of a gait aid. Five patients (25%) required continued use of a boot or brace during ambulation. Fourteen patients participated in the FAAM ADL survey. There were 6 patients lost to follow-up. The average FAAM score was 87 (range, 71.4-100). At last follow-up, most patients reported their overall function as "normal" or "nearly normal." Eradication of infection and satisfactory functional results can be attained after radical debridement, wound closure, and administration of culture-specific IV antibiotics.Level of evidenceLevel IV, retrospective case series.

Project description:BackgroundDuring the stance phase of running, the elasticity of the Achilles tendon enables the utilisation of elastic energy and allows beneficial contractile conditions for the triceps surae muscles. However, the effect of changes in tendon mechanical properties induced by chronic loading is still poorly understood. We tested the hypothesis that a training-induced increase in Achilles tendon stiffness would result in reduced tendon strain during the stance phase of running, which would reduce fascicle strains in the triceps surae muscles, particularly in the mono-articular soleus.MethodsEleven subjects were assigned to a training group performing isometric single-leg plantarflexion contractions three times per week for ten weeks, and another ten subjects formed a control group. Before and after the training period, Achilles tendon stiffness was estimated, and muscle-tendon mechanics were assessed during running at preferred speed using ultrasonography, kinematics and kinetics.ResultsAchilles tendon stiffness increased by 18% (P < 0.01) in the training group, but the associated reduction in strain seen during isometric contractions was not statistically significant. Tendon elongation during the stance phase of running was similar after training, but tendon recoil was reduced by 30% (P < 0.01), while estimated tendon force remained unchanged. Neither gastrocnemius medialis nor soleus fascicle shortening during stance was affected by training.DiscussionThese results show that a training-induced increase in Achilles tendon stiffness altered tendon behaviour during running. Despite training-induced changes in tendon mechanical properties and recoil behaviour, the data suggest that fascicle shortening patterns were preserved for the running speed that we examined. The asymmetrical changes in tendon strain patterns supports the notion that simple in-series models do not fully explain the mechanical output of the muscle-tendon unit during a complex task like running.

Dataset Information

Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon.

Publications

Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon.

Similar Datasets

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