Proteoglycan depletion of intact articular cartilage by retinoic acid is irreversible and involves loss of hyaluronate

Abstract

Intact sesamoid bones from bovine metacarpophalangeal joints were cultured with retinoic acid for 9 days and allowed to recover in control medium for up to 17 days. Retinoic acid (300 ng/ml) induced 91.8% inhibition of glycosaminoglycan (GAG) synthesis and 50.6% loss of sulfated GAGs from the cartilage. Retinoic acid also induced 38.2% loss of hyaluronate from the matrix. The synthesis and content of the large aggregating proteoglycan (aggrecan) were preferentially decreased compared with that of the small nonaggregating species. The aggrecan synthesized was similar to control aggrecan in size, aggregation capacity, and composition of its GAGs. GAG synthesis was almost completely restored in control medium within the next 6 days. The GAGs synthesized during recovery were slightly shorter than control GAGs and showed a higher ratio of chondroitin-6-sulfate over chondroitin-4-sulfate. Neither the proteoglycan content nor the hyaluronate content recovered within 17 days. The aggregation capacity of newly synthesized aggrecan was normal. However, the retention of proteoglycans synthesized in the recovery period was much lower in treated cartilage than in control cartilage (T1/2 of 17 and 38 days, respectively). In conclusion, the retinoic-acid-induced proteoglycan depletion was irreversible in spite of the restored synthesis of aggrecan with a normal aggregation capacity. The reduced retention of newly synthesized aggrecan during recovery might be caused by a lack of hyaluronate. This model seems suitable to study aspects of cartilage destruction and repair.

Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity

“…However, boney bridges were observed within the growth plates of these mice Figure 4—figure supplement 1B,D ), which are suggestive of prior growth plate trauma ( Wattenbarger et al, 2002 ; Xian et al, 2004 ). Given that alteration of cartilage matrix composition is a known effect of retinoids ( Campbell and Handley, 1987 ; Von den Hoff et al, 1993 ; Ostendorf et al, 1995 ), we speculate that these two mice represent an intermediate stage prior to the complete growth plate loss observed in all other palovarotene-treated Pdgfrα-R206H mice.…”

Proteoglycan metabolism and viability of articular cartilage explants as modulated by the frequency of intermittent loading

“…In studying the effect of dynamic mechanical forces on cartilage metabolism, many investigators have used in vitro systems since they offer important advantages over animal studies: in vitro models allow the study of cellular response to loading more directly, the flux of isotopic precursors and the passage of products can be determined in different compartments separately, and mechanical conditions can be manipulated more precisely. Direct mechanical forces have been applied to cartilage explants either statically 17,19 , as an often injurious impact load [13][14][15][16]18 , or as a repetitive cycle of forces, either applied continuously 17,[19][20][21][22] or intermittently [23][24][25][26][27][28][29][30][31][32][33] . Many of these loading protocols were chosen to simulate more closely the conditions cartilage might experience during normal or pathological joint function.…”

Effect of selected wound antiseptics on adult articular cartilage (bovine sesamoid bone) in the presence ofEscherichia coliandStaphylococcus aureus

“…Each concentration of antiseptic was studied in quadruplicate experiments. Each bsb was rinsed with 2x 10 ml PBS to remove adhering synovial fluid and was subsequently immersed in 9 ml Ham's F12 culture medium, supplemented with 0.1% (wlv) globulin-free bovine serum albumin (A-4161, Sigma, Germany), 0.2 mM sodium sulfate, and 10 ng/ml IGF-I (1-3769, Sigma, Germany) in a sterile 50-ml polypropylene test tube (3Ox I 15 mm, Greiner, Germany) [36,37].…”

“…For this purpose, a suitable in vitro model will be needed for both to estimate the effective concentration required for killing bacteria in the presence of articular cartilage and to characterize the biochemical response of chondrocytes to this treatment. Bovine sesamoid bones (bsb) from metacarpophalangeal joint have been employed for the investigation of chondrocyte metabolism in response to various stimuli [ 19,20,27,34,36,37] and were used in the present study. Ortliopaedic Research 23 (2005) [127][128][129][130][131][132][133] …”