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Muscular forces affect the glycosaminoglycan content of joint cartilage: unloading in human volunteers with the HEPHAISTOS lower leg orthosis.

ABSTRACT: Unloading alters the thickness of joint cartilage. It is unknown, however, to what extent unloading leads to a loss of glycosaminoglycans (GAGs) in the cartilage tissue. We hypothesized that muscle forces, in addition to axial loading, are necessary to maintain the joint cartilage GAG content of the knee and the upper and lower ankle.The HEPHAISTOS orthosis was worn unilaterally by 11 men (mean age 31 (23-50) years old) for 56 days. The orthosis reduces activation and force production of the calf muscles while it permits full gravitational loading of the lower leg. MRI measurements of the knee and ankle were taken before the intervention, during the intervention (on day 49), and 14 days after the end of the intervention. Cartilage segmentation was conducted semiautomatically for the knee joint (4 segments) and for the upper (tibio-talar) and lower (subtalar) ankle joints (2 segments each). Linear mixed-effects (LME) models were used for statistical analysis.8 volunteers completed the MRI experiment. In the lower ankle joint, differences in ?T1 were found between the end of the intervention and 14 days after (p = 0.004), indicating a decrease in GAG content after reloading. There were no statistically significant differences in ?T1 values in the knee and upper ankle joints.Our findings suggest that in addition to gravitational load, muscular forces affect cartilage composition depending on the local distribution of forces in the joints affected by muscle contraction.

SUBMITTER: Ganse B

PROVIDER: S-EPMC4443457 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Muscular forces affect the glycosaminoglycan content of joint cartilage: unloading in human volunteers with the HEPHAISTOS lower leg orthosis.

Ganse Bergita B Zange Jochen J Weber Tobias T Pohle-Fröhlich Regina R W Johannes Bernd B Hackenbroch Matthias M Rittweger Jörn J Eysel Peer P Koy Timmo T

Acta orthopaedica 20141124 3

<h4>Background and purpose</h4>Unloading alters the thickness of joint cartilage. It is unknown, however, to what extent unloading leads to a loss of glycosaminoglycans (GAGs) in the cartilage tissue. We hypothesized that muscle forces, in addition to axial loading, are necessary to maintain the joint cartilage GAG content of the knee and the upper and lower ankle.<h4>Patients and methods</h4>The HEPHAISTOS orthosis was worn unilaterally by 11 men (mean age 31 (23-50) years old) for 56 days. The ...[more]

PMID: 25417835

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Project description:Although short-term disuse does not result in measurable muscle atrophy, studies suggest that molecular changes associated with protein degradation may be initiated within days of the onset of a disuse stimulus. We examined the global gene expression patterns in sedentary men (n = 7, mean age Â± S.D = 22.1 Â± 3.7 yr) following 48h unloading (UL) via unilateral lower limb suspension and 24h reloading (RL). Biopsy samples of the left vastus lateralis muscle were collected at baseline, 48h UL, and 24h RL. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). Four genes were validated with qRT-PCR, and protein levels were measured with Western blot. Of the upregulated genes after UL, the most enriched functional group and highest ranked canonical pathway were related to protein ubiquitination. The oxidative stress response pathway was the second highest ranked canonical pathway. Of the downregulated genes, functions related to mitochondrial metabolism were the mostly highly enriched. In general, gene expression patterns following UL persisted following RL. qRT-PCR confirmed increases in mRNA for UPP-related E3 ligase Atrogin1 (but not accompanying increases in protein products) and stress response gene heme oxygenase-1 (HMOX, which showed a trend towards increases in protein products at 48h UL) as well as extracellular matrix (ECM) component COL4. The gene expression patterns were not readily reversed upon RL suggesting that molecular responses to short-term periods of skeletal muscle inactivity may persist after activity resumes. Biopsies were taken of the left vastus lateralis of healthy, sedentary men (N = 7) at baseline, immediately following 48h UL and 24h RL. A 5mm Berstrom biopsy needle was used. Biopsy samples were immediately snap-frozen in liquid nitrogen upon excision. All samples were stored at -80Â° C until analysis.

Dataset Information

Muscular forces affect the glycosaminoglycan content of joint cartilage: unloading in human volunteers with the HEPHAISTOS lower leg orthosis.

Publications

Muscular forces affect the glycosaminoglycan content of joint cartilage: unloading in human volunteers with the HEPHAISTOS lower leg orthosis.

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