Influence of aging on the synthesis and morphology of the aggrecans synthesized by differentiated human articular chondrocytes

Abstract

The declining aggrecan synthesis rates and the decreased capability of assembling large molecular size aggregates with increasing age in humans illustrates a progressive failure of the repair function of articular cartilage cells in humans.

Aged bovine chondrocytes display a diminished capacity to produce a collagen-rich, mechanically functional cartilage extracellular matrix

“…6). Verbruggen et al [38] noted that human chondrocytes (2-69 years old) do not proliferate at all once embedded in 1.5% autoclaved agarose, whereas Hauselmann et al [ 151 observed that human chondrocytes proliferate in 1% agarose, and proliferate more for younger donors, similar to our results ( Fig. 2A).…”

“…2A). Agarose concentration, site of donor tissue, method of digestion for cell isolation, frequency of medium change, ascorbic acid concentration, and the choice of serum supplement are all potential parameters that could lead to the discrepan- cies between the results of Verbruggen et al [38] versus Hauselmann et al [15] and the results of our study. Kamada et al [23] observed an age-dependence in proliferation of bovine chondrocytes embedded in alginate, but they noted that fetal chondrocytes proliferate less than aged ones, a result different from our study.…”

“…Hauselmann et al [15] also reported that chondrocytes from the youngest donor synthesized aggrecan molecules with higher average molecular weights. In contrast, Verbruggen et al [38] did not observe any proliferation for 2-to 69-year-old human chondrocytes embedded in agarose, but an increase in donor age correlated with reduced aggrecan synthetic rate and a smaller proportion of large aggregates. Loeser et al [26], by measuring sulfate and proline incorporation in alginate culture, found a mitigated response of macaque chondrocytes to IGF-1 with increasing animal age.…”

“…However, Kamada et al [23] in GAG content comparing aged to fetal chondrocytes, while we found only a slight decrease (-22%). It is possible that aggrecan, which is known to display reduced molecular size [I51 and decreased capability of assembling large molecular size aggregates [38] in aged tissue, is retained less in 1.2% alginate than in 2% agarose for bovine aged chondrocytes. We found a level of aggrecan loss to the medium similar to that of a previous study using agarose culture [3] (data not shown).…”

Age‐related expression patterns of Bag‐1 and Bcl‐2 in growth plate and articular chondrocytes

“…Decreased Bcl-2 expression with age is likely to be a contributing factor. It has also been demonstrated that there is decreased production of cartilage matrix proteins with age, especially in response to growth factors (Buckwalter et al, 1994;Bolton et al, 1999;Verbruggen et al, 2000). Maintenance of Bcl-2 expression may be important for maintaining cartilage matrix protein expression in vivo.…”