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Age-related changes in structure and extracellular matrix protein expression levels in rat tendons

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Abstract

The musculoskeletal system (muscle–tendon–bone) demonstrates numerous age-related changes, with modifications in tendons the least well studied, although increased predisposition to tendinopathy and rupture have been reported. In order to gain insights into the basis of age-associated increase in tendon injuries, we compared Achilles and tibialis anterior tendons and myotendinous junctions (MTJs) from 3- to 5- and 22- to 25-month-old rats for underlying structure and composition. Significant decreases were observed by qRT-PCR for collagen I, III, and V mRNA expression in tendons of old rats, but immunostaining detected no apparent differences in collagen I and V expression on the protein level. Tendons of old compared with young rats had decreased mRNA expression levels of proteoglycan 4 (PRG4) and elastin (Eln), but no differences in the mRNA expression of connective tissue growth factor, TGF-beta 1, or stromal cell-derived factor 1. For PRG4, immunostaining showed good correlation with qRT-PCR results. This is the first study to show reductions in PRG4 in tendons and MTJs of old rats. Decreased PRG4 expression in tendons could result in increased tendon stiffness and may be associated with decreased activity in the elderly. The diminished collagen mRNA expression in combination with decreased PRG4 and Eln mRNA expression may be associated with increased risk of tendon injury with aging.

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Abbreviations

CTGF:

Connective tissue growth factor

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

Eln:

Elastin

IGF:

Insulin-like growth factor

FGF:

Fibroblast growth factor

GDF:

Growth differentiation factor

LOX:

Lysyl oxidase

MTJs:

Myotendinous junctions

PRG4:

Proteoglycan 4

SDF1:

Stromal cell-derived factor 1

TBA:

Tibialis anterior muscle

TGFb:

Transforming growth factor beta

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Acknowledgments

This study was supported by NIH Grant AR-055624 (SVB) and IUSM-Northwest (TYK).

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Correspondence to Tatiana Y. Kostrominova.

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Supplemental Fig. 1

Evaluation of paxillin, talin and collagen XXII expression at MTJs of young rats. Immunostaining of MTJ regions of TBA tendons from young rats with antibodies against paxillin, talin and collagen XXII (red in A–C). DAPI (blue) was used to co-stain the nuclei. WGA-fluorescein (green in A and C) and anti-collagen type I antibodies (green in B) were used to visualize connective tissue. Arrows indicate increased protein accumulation at the muscle/tendon border. (PDF 2212 kb)

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Kostrominova, T.Y., Brooks, S.V. Age-related changes in structure and extracellular matrix protein expression levels in rat tendons. AGE 35, 2203–2214 (2013). https://doi.org/10.1007/s11357-013-9514-2

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