Abstract
Knee cartilage is in an aqueous environment filled with synovial fluid consisting of water, various nutrients, and ions to maintain chondrocyte homeostasis. Aquaporins (AQPs) are water channel proteins that play an important role in water exchange in cells, and AQP1, -3, and -4 are known to be expressed predominantly in cartilage. We evaluated the changes in AQP expression in chondrocytes from human knee articular cartilage in patients of different ages and identified the key factor(s) that mediate age-induced alteration in AQP expression. The mRNA and protein expression of AQP1, -3 and -4 were significantly decreased in fibrocartilage compared to hyaline cartilage and in articular cartilage from older osteoarthritis patients compared to that from young patients. Gene and protein expression of AQP1, -3 and -4 were altered during the chondrogenic differentiation of C3H10T1/2 cells. The causative factors for age-associated decrease in AQP included H2O2, TNFα, and HMGB1 for AQP1, -3, and -4, respectively. In particular, the protective effect of AQP4 reduction following HMGB1 neutralization was noteworthy. The identification of other potent molecules that regulate AQP expression represents a promising therapeutic approach to suppress cartilage degeneration during aging.
Highlights
Knee cartilage is in an aqueous environment filled with synovial fluid consisting of water, various nutrients, and ions to maintain chondrocyte homeostasis
To determine whether AQPs are associated with cartilage physiology, we initially analyzed the expression of AQPs in cartilage tissues isolated from patients who were surgically treated for osteoarthritis of the knee by arthroscopic surgery or total knee replacement surgery (Fig. 1a)
As aging is one of the most deleterious factors for cartilage degenerations, we examined the expression of AQPs in cartilage tissues from different age groups
Summary
Knee cartilage is in an aqueous environment filled with synovial fluid consisting of water, various nutrients, and ions to maintain chondrocyte homeostasis. The mRNA and protein expression of AQP1, -3 and -4 were significantly decreased in fibrocartilage compared to hyaline cartilage and in articular cartilage from older osteoarthritis patients compared to that from young patients. Aging leads to various changes in chondrocytes and ECM of articular cartilage characterized by cellular senescence, proteolysis, advanced glycation, calcification, and even tissue d estruction[14]. These intra- and extracellular changes are driven by the dysfunction of cellular homeostasis. (d) Western blot analyses for AQP1, -3 and -4 protein expression between intact hyaline cartilage and fibrocartilage (n = 6 per group). Data represent means ± standard errors of the means. *P < 0.05
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