Age‐related changes of tendon fibril micro‐morphology and gene expression

Abstract

Aging is hypothesized to be associated with changes in tendon matrix composition which may lead to alteration of tendon material properties and hence propensity to injury. Altered gene expression may offer insights into disease pathophysiology and thus open new perspectives toward designing pathophysiology‐driven therapeutics. Therefore, the current study aimed at identifying naturally occurring differences in tendon micro‐morphology and gene expression of newborn, young and old horses. Age‐related differences in the distribution pattern of tendon fibril thickness and in the expression of the tendon relevant genes collagen type 1 (Col1), Col3, Col5, tenascin‐C, decorin, tenomodulin, versican, scleraxis and cartilage oligomeric matrix protein were investigated. A qualitative and quantitative gene expression and collagen fibril diameter analysis was performed for the most frequently injured equine tendon, the superficial digital flexor tendon, in comparison with the deep digital flexor tendon. Most analyzed genes (Col1, Col3, Col5, tenascin‐C, tenomodulin, scleraxis) were expressed at a higher level in foals (age ≤ 6 months) than in horses of 2.75 years (age at which flexor tendons become mature in structure) and older, decorin expression increased with age. Decorin was previously reported to inhibit the lateral fusion of collagen fibrils, causing a thinner fibril diameter with increased decorin concentration. The results of this study suggested that reduction of tendon fibril diameters commonly seen in equine tendons with increasing age might be a natural age‐related phenomenon leading to greater fibril surface areas with increased fibrillar interaction and reduced sliding at the fascicular/fibrillar interface and hence a stiffer interfascicular/interfibrillar matrix. This may be a potential reason for the higher propensity to tendinopathies with increasing age.

Tenascin-C: Friend or Foe in Lung Aging?

“…In adult lung, a weak expression of TNC was consistently reported in airway smooth muscle and basal cell layers, while expression in the parenchyma was described as very faint and inconsistent by some authors ( Koukoulis et al, 1991 ; Natali et al, 1991 ; Kaarteenaho-Wiik et al, 2001 ; Liesker et al, 2009 ; Lofdahl et al, 2011 ). The role of TNC in normal aging was explored essentially in tissues submitted to high tensile stress such as the skin ( Choi et al, 2020 ), cardiac muscle ( Sato and Shimada, 2001 ), ligament/tendon ( Fujii et al, 1993 ; Veronesi et al, 2015 ; Ribitsch et al, 2020 ) or even cartilage ( Gruber et al, 2002 , 2011 ). In the lung, a single report comparing 24 to 8 months old decellularized mouse lung scaffolds showed that aging was linked to an increase in collagen and collagen-related proteins, and that this increase was preceded by an increase in TNC and osteopontin expression and associated with an increase in the number of senescent cells ( Calhoun et al, 2016 ).…”

Age and Intrinsic Fitness Affect the Female Rotator Cuff Tendon Tissue

“…This can be seen as an effect of normal (natural) aging. Collagen type I is the major structural component of the tendon, and its age-dependent repression was also reported for rat [ 15 ], horse [ 16 ] and for human tendons [ 17 ]. ELN is the core protein of elastic fibers and ensures elastic stretching and recoiling of tissue, cooperating with collagen for tensile resistance [ 18 ].…”

“…TNMD is a tendon-specific marker known to be important for tendon maturation with key implications for the residing tendon stem/progenitor cells. An age-dependent down-regulation of Tnmd was described in horse tendons [ 16 ] but also in mice intervertebral discs and has been postulated as a risk factor for age-related degeneration [ 23 ]. Regarding the healing of rotator cuff tears it has already been shown that the sustained delivery of TGFB3 accelerated the healing process [ 24 ] and in mouse Achilles’ tendons canonical TGFβ signaling has a functional role in tendon regeneration [ 25 ].…”

Anti-inflammatory and antiaging properties of chlorogenic acid on UV-induced fibroblast cell

“…While CA could potentially decrease the levels of ROS, IL-1β, and TNF-a, the measurement of COL-3 gene expression can also be conducted to determine the repairing effect of CA toward aging. COL-3 gene is related to the pattern of tendon fibril thickness and is more abundant in younger individuals than aged individuals of the animal model (Ribitsch et al, 2019). UV exposure could also decrease the COL-3 gene expression level (Chen et al, 2019).…”