Mechanical loading plays an essential role in both tendon development and degradation. However, the underlying mechanism of how tendons sense and response to mechanical loading remains largely unknown. SPARC, a multifunctional extracellular matrix glycoprotein, modulates cell extracellular matrix contact, cell-cell interaction, ECM deposition and cell migration. Adult mice with SPARC deficiency exhibited hypoplastic tendons in load-bearing zone. By investigating tendon maturation in different stages, we found that hypoplastic tendons developed at around postnatal 3 weeks when the mice became actively mobile. The in vitro experiments on primary tendon derived stem cells demonstrated that mechanical loading induced SPARC production and AKT/S6K signalling activation, which was disrupted by deleting SPARC causing reduced collagen type I production, suggesting that mechanical loading was harmful to tendon homeostasis without SPARC. In vivo treadmill training further confirmed that increased loading led to reduced Achilles tendon size and eventually caused tendon rupture in SPARC-/− mice, whereas no abnormality was seen in WT mice after training. We then investigate whether paralysing the hindlimb of SPARC-/− mice using BOTOX from postnatal 2 weeks to 5 weeks would delay the hypoplastic tendon development. Increased patellar tendon thickness was shown in SPARC-/− mice by reducing mechanical loading, whereas opposite effect was seen in WT mice. Finally, we identified a higher prevalence of a missense SNP in the SPARC gene in patients who suffered from a rotator cuff tear. In conclusion, SPARC is a mechano-sensor that regulates tendon development and homeostasis.

Introduction

Metabolic disorders are among known risk factors for tendinopathies or spontaneous tendon ruptures. However, the underlying cellular and molecular mechanisms remain unclear. We have previously shown that human and rat tendon cells produce and secrete insulin upon glucose stimulation. Therefore, we hypothesize that nutritional glucose uptake affects tendon healing in a rat model.

Introduction

The ability of tendons to withstand stress generally decreases with age, often resulting in increased tissue degeneration and decreased regeneration capacity. However, the underlying molecular and cellular mechanisms of tendon senescence remain poorly characterized. Therefore, the aim of the current study was to identify genes showing an age-dependent altered expression profile in tendons.

The need for supplementary screw fixation in acetabular revisions is still widely debated. We carried out 439 acetabular revisions over an eight-year period. In 171 hips with contained or small segmental defects, the Morscher press-fit cup was used. These revisions were followed prospectively. No screws were used for additional fixation.

A total of 123 hips with a mean follow-up of 7.4 years (5 to 10.5) were available for clinical and radiological review. There was no further revision of a press-fit cup for aseptic loosening. Radiological assessment revealed osteolysis in three hips. Of the original 171 hips there was cranial and medial migration of up to 6 mm at two years in 44 (26%). No further migration was seen after the second post-operative year. Acetabular revision without screws is possible with excellent medium-term results in well selected patients.