Effects on joint structure or metabolism
Effects changes on joint structure, or metabolism were investigated in all in vivo studies through outcomes such as analysis of SF content and volume, histology, histochemistry, and cartilage metabolism.
SF analysis was included in seven studies (Saari et al., 1992; Frisbie et al., 1997; Frisbie et al., 1998; Todhunter et al., 1998; Robion et al., 2001; Céleste et al., 2005; Knych et al., 2017). In three studies, MPA decreased SF volume in joints (Frisbie et al., 1998; Robion et al., 2001) with no or transient changes in WBC counts and total solid content (Saari et al., 1992; Todhunter et al., 1998; Robion et al., 2001); however, significant increases in TP were found by Frisbie et al. (1998). MPA injections also increased SF concentrations of GAG, PG, and HA in two studies (Saari et al., 1992; Frisbie et al., 1998).
When TA was evaluated, no significant changes were found in TP or WBC counts (Céleste et al., 2005; Knych et al., 2017), and no significant changes in color were found in two studies (Céleste et al., 2005; Knych et al., 2017). One study noted significantly higher scores (demonstrating more changes) in SF color compared to controls (Frisbie et al., 1997). Mucin content was decreased, while GAG and HA concentrations were significantly increased in TA-treated joints (Frisbie et al., 1997).
Biomarker concentrations in SF after MPA and TA were also evaluated (Robion et al., 2001; Céleste et al., 2005). Both corticosteroids were found to increase aggrecan 846 and KS epitopes – suggesting an increase in PG release. CPII, on the other hand, was found to be decreased after the second MPA injection (suggesting inhibition of collagen synthesis), while increases were found after TA (Robion et al., 2001; Céleste et al., 2005). TA also increased concentrations of C1,2C –, which would reflect collagen degradation (Céleste et al., 2005).
Two studies evaluated Gene expression in SF for TA and IPA (Knych et al., 2017; Knych et al., 2018). MMP-1 and -9 were elevated up to 14 days and 96 h, respectively, while collagen genes were downregulated from 12 h to 42 days after TA IA injection (Knych et al., 2017). When IPA was evaluated, only a transient increase in MMPs followed by a persistent decrease (MMP-1 and -9) was found for up to 42 days with no significant changes in the expression of collagen genes (Knych et al., 2018).