The effects of maturation and aging on the rotator cuff tendon‐to‐bone interface

Abstract

Rotator cuff tendon injuries often occur at the tendon‐to‐bone interface (i.e., enthesis) area, with a high prevalence for the elderly population, but the underlying reason for this phenomenon is still unknown. The objective of this study is to identify the histological, molecular, and biomechanical alterations of the rotator cuff enthesis with maturation and aging in a mouse model. Four different age groups of mice (newborn, young, adult, and old) were studied. Striking variations of the entheses were observed between the newborn and other matured groups, with collagen content, proteoglycan deposition, collagen fiber dispersion was significantly higher in the newborn group. The compositional and histological features of young, adult, and old groups did not show significant differences, except having increased proteoglycan deposition and thinner collagen fibers at the insertion sites in the old group. Nanoindentation testing showed that the old group had a smaller compressive modulus at the insertion site when compared with other groups. However, tensile mechanical testing reported that the old group demonstrated a significantly higher failure stress when compared with the young and adult groups. The proteomics analysis detected dramatic differences in protein content between newborn and young groups but minor changes among young, adult, and old groups. These results demonstrated: (1) the significant alterations of the enthesis composition and structure occur from the newborn to the young time period; (2) the increased risk of rotator cuff tendon injuries in the elderly population is not solely because of old age alone in the rodent model.

Compositional, Structural, and Biomechanical Properties of Three Different Soft Tissue–Hard Tissue Insertions: A Comparative Review

“…30 For the tendon insertion, zone 2 is mainly composed of fibrochondrocytes, types II and III collagen, PGs (aggrecan, decorin, biglycan, versican and chondroadherin), with a small number of types I, IX and X collagen. 4,22,23,42,43 Fibroblasts are distributed around the Type I collagen in the tendon insertion. 23 The organization of chondrocyte lacunae size across zone 2 is in the distance dependent on the pattern.…”

“…The crystalline ordering within the apatite increases concomitantly with the degree of mineralization . At different ages, the tendon insertion components have also changed since the collagen, GAG, and DNA contents of the newborn are significantly higher than others . Collagen distribution and proteoglycan content will also change as the ligament insertion remodels with age …”

Creating an Optimal In Vivo Environment to Enhance Outcomes Using Cell Therapy to Repair/Regenerate Injured Tissues of the Musculoskeletal System

“…While many tissues function in the context of a mechanical environment, such as the lung, skin, and the cardiovasculature system, tissues of the musculoskeletal system function in a variety of compressive, shear or tensile environments, and their complex structures reflect such requirements in unique and specialized environments. While the composition and functioning of tissues, such as tendons, ligaments, menisci and articular cartilage can undergo changes with aging [ 2 , 72 , 73 , 74 ], it is not known in detail if they have evolved to their optimum to last for >80–90 years. It is clear that structure and function relationships are critical to the performance of functional activities.…”

“…While the above discussion has focused on repair of articular cartilage, some of the principles discussed can also be applied to the healing of other connective tissues of the MSK system, including menisci, intravertebral discs (IVD), as well as ligaments and tendons. In the case of tendons, tendons in different locations exhibit different properties [ 185 ], tendon properties can change with aging [ 74 , 186 , 187 ] and some tendons, such as the supraspinatus, can undergo age-related degeneration without overt symptoms [ 188 , 189 , 190 ]. Thus, cell therapy treatment could be envisioned to address tendinopathies rather than overt ruptures.…”

NAMPT-Improved Mitochondrial Function Alleviates Degenerative Rotator Cuff Tendinopathy in Aged Mice

“…The effects of aging on the rotator cuff have previously been studied mainly at the tendon-to-bone interface 34,35 . However, most tears are found in tendon tissues that are proximal to the enthesis, instead of at the enthesis itself 28 .…”