The age-related cartilage wear that occurs in macroscopically normal joints and is evident at the superficial zone indicates that the wear-protective function of synovial fluid (SF) and wear resistance of cartilage changes with aging, and may lead to osteoarthritis (OA). One possible reason for these changes occurring in the knee is age- and disease-related deterioration in the quality of SF lubricant. Hyaluronan (HA) is a primary lubricant molecule in SF that adsorbs to the articular surface. The cartilage-on-cartilage, friction-lowering properties of HA depend on its concentration and molecular mass (Mr). Improved lubrication properties are found in HA with higher Mr. Human synovial fluid (hSF) HA concentration changes little with age, or tends to decrease between ages 28 and 40 years, but little is known about the effects of age- and OA-related degeneration. HA concentration is lower in patients with OA than in those with normal knees, with a shift toward HA with lower Mr; however, the age-associated changes are unclear in the content and Mr of HA in hSF in knee joints of patients without OA.
Michele M. Temple-Wong, PhD, Department of Bioengineering, University of California-San Diego, La Jolla, and colleagues sought to determine whether the concentration and quality of HA in SF was similar in left and right knees, if it exhibited similar age-associated trends, and if it varied with age and the grade of joint degeneration. They found a possible relationship between the age-related increase in cartilage wear in non-OA joints and changes in HA content and quality of SF.
The study authors analyzed hSF in knee joints without OA. The hSF was aspirated from 1 or both knee joints (n = 48) of 28 human cadavers within 72 hours of death. The donors did not have OA, based on exclusion criteria of previous knee arthritis or trauma, body mass index (BMI) >30 kg/m2, and macroscopic evidence of osteophytes, full thickness erosion, or severe degeneration. Donors were selected to mirror an even distribution of age (23-91 years) and sex (12 men, 16 women), and a BMI of 12 to 30 kg/m2. Each hSF sample was analyzed for the concentrations of protein, HA, and HA in Mr ranges of 2.5 to 7 MDa, 1 to 2.5 MDa, 0.5 to 1 MDa, and 0.03 to 0.5 MDa. Similarities in overall joint grade and hSF properties of the left and right knees were analyzed by reduced major axis regression, paired t tests, and a Bland-Altman analysis.
"The results of the present study delineated characteristics of HA in hSF from knees that exhibited early-stage age-associated deterioration but not OA. HA concentration was strikingly similar between left and right knees of the same cadaveric donor (R2 = 0.67), and decreased substantially with age (R2 = 0.21)," Dr Temple-Wong and colleagues noted.
They also found that HA concentration in each of the Mr ranges decreased at an average of approximately 11.3% per decade of age (R2 = 0.15-0.24). Joint grade also varied with age, increasing approximately 10.5% per decade of age. The similar age-associated decrease in concentration of HA in each of the Mr ranges is a novel result that may be of interest to those studying joint mechanics and mechanobiology. The authors noted that the decrease in high-Mr HA may be particularly significant, because large molecules contribute to boundary lubrication between articular cartilage-on-cartilage surfaces, where HA may interact with the PRG4 gene. The age-related changes may be a result of several factors, such as HA anabolism, catabolism, and transport.
Dr Temple-Wong and colleagues concluded that the age-related decrease in high-Mr HA may allow modulation to restore hSF to normal lubricant molecule concentrations patients had when they were young. The age-related concentration decrease of HA in hSF in patients without OA, and the association of decreased HA in SF with increased friction between cartilage surfaces, suggests that this relationship may be an important aspect in the age-related wear of knee articular cartilage.
- Temple-Wong MM, Ren S, Quach P, et al. Hyaluronan concentration and size distribution in human knee synovial fluid: variations with age and cartilage degeneration. Arthritis Res Ther. 2016;18:18.