IN-VITRO EFFECTS OF METHOTREXATE ON HUMAN ARTICULAR-CARTILAGE AND BONE-DERIVED OSTEOBLASTS

Conflicting data have been published on whether low-dose methotrexate (MTX) treatment of rheumatoid arthritis (RA) is able to slow down radi ological joint damage, i.e. retard the destruction of articular cartil age and (subchondral) bone. We studied the effects of MTX on proteogly can (PG) turnover and interleukin-1 (IL-1)- and RA mononuclear cell (R A-MNC)-induced cartilage damage in human articular cartilage tissue cu ltures, and the effects of MTX on basal and RA-MNC-influenced prolifer ation and differentiation of osteoblasts in cultures of human bone-der ived osteoblasts. MTX exerted no direct effect on cartilage nor did MT X influence IL-1- or RA-MNC-induced cartilage damage, despite strong s uppression of basal as well as mitogen- and antigen-induced RA-MNC pro liferation. MTX induced strong inhibition of osteoblast proliferation, but did not significantly interfere with osteoblast differentiation ( i.e. alkaline phosphatase activity). RA-MNC-enhanced proliferation and differentiation of osteoblasts were abolished by MTX. These results s uggest that if MTX is able to induce retardation of radiological progr ession in RA, this is not based on an initial direct effect of MTX on cartilage as measured by PG turnover, nor on an initial inhibition of IL-1- or RA-MNC-induced cartilage damage. However, longstanding MTX-in duced inhibition of RA-MNC proliferation may lead to reduction of the catabolic activity involved in cartilage destruction. On the other han d, long-term inhibition of osteoblast proliferation may eventually lea d to decreased bone formation and osteopenia. Whether this will turn o ut to be a problem of clinical importance in the treatment of RA has t o be established.