Hyaluronan does not affect cytokine and chemokine expression in osteoarthritic chondrocytes and synoviocytes.
OBJECTIVE
Many studies have evidenced the clinical efficacy of hyaluronan (HA) in the treatment of osteoarthritis (OA). However, human and animal studies have described proinflammatory effects of HA on cells not involved in OA. We therefore investigated whether different molecular weight HA preparations can affect proinflammatory cytokine (IL1beta and TNFalpha) or chemokine (IL8, MCP-1 and RANTES) expression in human chondrocytes and synoviocytes isolated from OA patients.


METHODS
Human chondrocytes and synoviocytes were cultured in vitro in the presence or absence of three different purified HA pharmaceutical preparations (1x10(6) Kd, 5x10(5) Kd and 6.5x10(4) Kd) and assessed for the production of proinflammatory cytokines and chemokines and their mRNA expression.


RESULTS
basal conditions, both chondrocytes and synoviocytes produce only MCP-1 and IL8, along with low quantities of IL1beta and TNFalpha, but not RANTES. IL8 production was generally about 100 times higher in chondrocytes than in synoviocytes, while MCP-1 was roughly twice as high in synoviocytes than in chondrocytes. At the mRNA level, expression of IL1beta, TNFalpha, IL8, MCP-1 and RANTES did not change in the presence of the three HA preparations either in synoviocytes or in chondrocytes with respect to basal condition. None of the three different HA preparations significantly affected production of IL8 or MCP-1.


CONCLUSIONS
These data demonstrate that preparations of HA of the same origin but with different MWs do not induce proinflammatory cytokines and chemokines expressed by chondrocytes and synoviocytes that are either directly or indirectly involved in OA progression.
Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy.
G
G
Lisignoli
F
F
Grassi
A
A
Piacentini
B
B
Cocchini
G
G
Remiddi
C
C
Bevilacqua
A
A
Facchini
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D018925:Chemokines / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D006820:Hyaluronic Acid