Influence of age on the cell biological characteristics and the stimulation potential of male human tenocyte-like cells

Abstract

The incidence of rotator cuff tears and recurrent defects positively correlate with patient age. However, this observation has never been analysed at the cellular level. The present study aims to better understand this correlation by investigating cellular characteristics of rotator cuff tenocytes of different age groups. Additionally, previous studies reported on stimulating effects of Bone Morphogenetic Protein (BMP)-2 and BMP-7 on tenocytes. Thus, the second aim was to investigate, whether the stimulation potential of tenocytes demonstrates age-related differences. Tenocyte-like cells from supraspinatus tendons of young and aged male patients were analysed for the following cell biological characteristics: cell density, cell growth, marker expression, collagen-I protein synthesis, stem cell phenotype, potential for multipotent differentiation and self-renewal. To analyse the stimulation potential, cells were treated with BMP-2 and BMP-7 in 2D-/3D-cultures. Measured parameters included cell activity, marker expression and collagen-I protein synthesis. An effect of age was seen for cell growth and stem cell potential but not on extracellular matrix level. Cells from both groups responded to BMP-7 by increasing cell activity, collagen-I expression and protein synthesis. BMP-2 led to smaller increases in these parameters when compared to BMP-7. In general, 3D-cultivation improved the stimulation compared to 2D-culture. The cell biological characteristics of tenocyte-like cells, considered important for successful restoration of the tendon-bone unit, were inferior in elderly donors. This may help explain higher rates of recurrent defects seen in elderly patients. Regarding the stimulation potential, on a cellular level young and aged patients may benefit from biological augmentation with BMPs.

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

“…It is still unclear whether or not there is a specific factor(s) involved in the biomechanical changes of tendons due to ageing, and this is highly debated in the literature. 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.…”

Hyaluronic acid increases tendon derived cell viability and proliferation in vitro: comparative study of two different hyaluronic acid preparations by molecular weight

“…Non-traumatic rotator cuff tear is the most common shoulder joint disease and it has age-associated incidence, since it is favored by the co-presence of metabolic diseases such as diabetes, thyroid disorders and hypercholesterolemia [1][2][3][4] . Conservative treatment of tendinopathies has been increasingly supported by scientific evidence over the last twenty years 5 .…”

“…During tendinopathy and tendon acute rupture, a higher incidence of tenocyte apoptosis occurrence and decreased collagen synthesis has been reported 8 . The failure of the healing response may occur in genetically-predisposed patients, decreasing the resistance of tendon structures to mechanical load, resulting eventually in tendinopathy, or a tendon tear 4,9,10 . Hyaluronic acid (HA) (or "hyaluronan", or "sodium hyaluronate preparation") is a high molecular weight glycosaminiglycan, consisting on the repetition of a disaccharide unit composed by N-acetyl-glucosamine and a β-glucuronic acid 11 .…”

Role of Metalloproteinases in Tendon Pathophysiology

“…In fact, this structural arrangement and the tenocyte interrelationships are also affected by age [13], clearly showing a different tendon structure in newborn, young and adult individuals (Fig. 2) [14].…”