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

Abstract

The musculoskeletal system (muscle-tendonbone) 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.

Knee stability after anterior cruciate ligament reconstruction in patients older than forty years: comparison between different age groups

“…Some authors found a different collagen type I and type III expression in tendons of young people compared with the elderly [1,4,10,17], whereas other authors found no difference [11]. In the study by Kostrominova and Brooks [12], decreased expression in elastin (ELN) messenger RNA (mRNA) (the main property of ELN is the ability to deform reversibly with little force and without loss of strength) and in proteoglycan 4 (PRG4) (a glycoprotein with lubricating properties) in elderly tendons was also found, and this could be SD standard deviation responsible for the increased tendon stiffness. Another study [22] shows an increase in metalloproteinase-2 (MMP-2) and MMP-9 activity.…”

Aging affects mechanical properties and lubricin/PRG4 gene expression in normal ligaments

“…Interestingly, support for this conclusion has been well-established when considering the role of lubricin/PRG4 in tendons. Various preclinical models (canine, bovine, caprine, rat) have been used to demonstrate the presence of lubricin/PRG4 on both the surface of tendons, as well as the interface between collagen fascicles (Sun et al, 2006;Lee et al, 2008;Funakoshi et al, 2008;Kostrominova and Brooks, 2013). Hayashi et al (2013) provided biomechanical evidence for the role of lubricin/PRG4 in mouse deep digital flexor tendons by comparing tendon gliding resistance in heterozygous (Prg4 þ/þ ), wild type (Prg4 þ/ À ), and knockout (Prg4 À /À ) mice.…”

Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies

“…84 Kostrominova and Brooks observed an age-associated decrease in mRNA (mRNA) coding for collagen types I, III, and V, elastin, and proteoglycan 4 in murine tendons. 85 It was found that age correlated directly with increased MMP2, MMP7, tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP-2, and TIMP-4 while MMP9 concentration decreased with age. 86 mRNA levels of MMP2 and MMP9, as well as MMP2 and MMP9 activity, increased with age in tendons.…”