gms | German Medical Science

Objectives: Mechanical forces are vital for the maintenance and function of tendon tissue. Investigating the impact of mechanical loading on tendons in animal models might provide important information on in vivo tendon mechanobiology. A well-established in vivo mouse model showed improved bone formation in the loaded compared to the non-loaded tibiae [1]. The present study aimed to investigate the suitability of this model to examine structural and molecular changes in the tendon.

Methods: The left tibiae of a 10-week old female BALB/c mice (n=14) were subjected to axial cyclic compressive loading (10N, εmax=2000µε at tibial mid-shaft determined by strain gauging, 216 cycles/day at 4 Hz) on a Testbench ElectroForce (LM1, Bose) for 3 weeks (M-F) and the right tibiae served as the internal non-loaded control (approval: LAGeSo Berlin, G0027/15). Mice were sacrificed at day 20 and the Achilles tendons were dissected. The Achilles tendons were investigated for structural changes by histological analysis (n=8) and on the molecular level by quantitative Real-time PCR (n=6).

Results and conclusion: Histological analysis showed no significant differences between the loaded and non-loaded Achilles tendon regarding cell size, collagen content and anisotropy of collagen fibers. Moreover, no signs of degeneration such as fiber disorganization and increased cell number were observed. Gene expression analysis of the in vivo loaded Achilles tendon revealed significantly increased levels of type I and III collagen, Matrix metalloprotease 2 (MMP2) and Mechano-growth factor (MGF). No significant changes were detected for the tenocyte-related genes Scleraxis and Tenomodulin.

This study showed for the first time that mechanical stimulation used in a set-up to investigate bone loading induced no changes in the tendon tissue structure, however, the effects on the molecular level were significant.

Significant increases of type I and III collagen and MMP2 in the loaded tendon indicate changes in the extracellular matrix, which were not dramatic enough to induce histologically visible degeneration. MGF is a splice variant of IGF-1 (IGF-IEb) and was discovered in muscle responding to mechanical stimuli, potentially facilitating repair and maintenance after injury. The increase observed in the present study supports the results of another study showing that up-hill running induced superior mechanical properties in rat tendons [2].

This experimental set-up allows the investigation of mechanical forces without inducing degeneration, and will provide further knowledge in tendon mechanobiology, which is important for the development of rehabilitation programs.