Effects of alendronate on a disintegrin and metalloproteinase with thrombospondin motifs expression in the developing epiphyseal cartilage in rats.

ABSTRACT

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) have been reported to play a role in the degradation of aggrecan, a major component of cartilage. This study was performed to examine the effects of alendronate on the expression of ADAMTS in developing femoral epiphyseal cartilage. Primary cultured chondrocytes from this cartilage were treated with alendronate in vitro and postnatal day 1 rats were injected subcutaneously with alendronate (1 mg/kg) every second day in vivo. The number of cultured chondrocytes and their aggrecan mRNA levels were unaffected by the alendronate treatment at 10(-6) to 10(-4) M concentrations. The mRNA levels of ADAMTS-1, -2 and -9 in chondrocytes were also unaffected. However, the levels of ADAMTS-5 and -4 were reduced significantly by the same treatment. The thickness of the proliferating chondrocyte layers and the aggrecan mRNA levels in the epiphysis were unaffected by the alendronate treatment in vivo. However, the hypertrophied chondrocyte layers became significantly thicker, and the size of the secondary ossification centre was reduced significantly by the same treatment (P < 0.05). Both ADAMTS-4 and -5 mRNA expressions were also reduced significantly in vivo. The immunoreactivity against ADAMTS-4 was seen in hypertrophied chondrocytes and reduced significantly by the alendronate treatment. These results suggested that alendronate can inhibit the degradation of aggrecan in the articular cartilage by downregulating the expression of matrix enzymes such as ADAMTS-4 and -5.