Table II.

Summary of molecular mechanisms of fibroblastic synoviocytes (inflammation, migration, and invasion).

Molecules	Mode of action	Species	Dose		Ref
			In vivo	in vitro
Endogenous factors
Chemerin	Activation of cytokine production, MMP-3 expression, and FLS migration	RA-FLS		10 to 50 μM	113
DKK-1 and FAK	Enhancement of FLS migration	RA-FLS			114
GRP	Enhancement of FLS invasion through Akt activation	RA-FLS		10 μM	115
Class 3 semaphorins	Activation of RAC1 and increasing effect on RA-FLS invasion	RA-FLS		10 μM	116
HIP-1	Enhancement of FLS migration	RA-FLS			117
Adrenomedullin	Increase of FLS adhesion	RA-FLS		100 nM	118
HDAC	Increase of IL-6 and IL-1β expression	RA-FLS, CIA mice			119
FSTL1	Enhancement of MMP expression and invasion of FLS	RA-FLS		1 to 5 μg/ml	120
Cadherin-11	Enhancement of FLS adhesion and proliferation	RA-FLS			121,122
Anti-CCP antibody	Increase of FLS migration through PI3K activation	RA-FLS		1 μg/ml	123
Synthetic compounds
CA-074Me	Inhibition of cathepsin B with decrease of MMP-2, F-actin, and phosphorylation of p38 MAPK/JNK	RA-FLS		10 μM	124
Natural compounds
C3G	Inhibition of LPS-induced IL-6 and IL-1β production	RA-FLS, CIA mice	50 mg/kg	10 to 40 μM	125
Oxymatrine	Protection of joint destruction	RA-FLS, CIA mice	100 mg/kg	10 to 100 μM	126

C3G, cyanidin-3-glucoside; CIA, collagen-induced arthritis; DKK-1, Dickkopf-1; FAK, focal adhesion kinase; FLS, fibroblastic synoviocytes; FSTL1, follistatin-like protein 1; GRP, gastrin-releasing peptide; HDAC, histone deacetylase; HIP-1, Huntingtin-interacting protein-1; IL, interleukin; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinases; MMP, matrix metalloproteinase; PI3K, phosphoinositide 3-kinase; RA, rheumatoid arthritis.