Bisphosphonate가 무릎관절 연골판 뼈 형성에 미치는 영향
Effects of bisophosphonate on the ossification of growth plate of the knee joint in rats
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Bisphosphonate는 뼈 흡수를 억제하는 작용을 가지며 그 기전을 밝히는 연구가 시도되고 있다. 연골 흡 수는 연골파괴세포(chondroclast)에 의하며 연골파괴세포는 뼈파괴세포(osteoclast)와 같은 분화 및 운명을 겪게 되므로 bisphosphonate가 연골 흡수 및 발육 과정에 영향을 미칠 것으로 가정된다. 뼈끝연골판(epiphyseal plate)은 긴 뼈의 길이 성장에 중요한 역할을 하며 뚜렷한 연골세포층을 형성하고 있고, 뼈발생중심이 출현하기 때문에 뼈 의 성장을 연구하는데 좋은 모델이 되고 있다. 본 연구는 성장기 흰쥐 뼈끝연골판에서 bisphosphonate 제제인 alendronate가 연골 흡수 및 골화 과정에 미치는 영향을 구명하고자 시도되었다. 생후 10일간 약물투여한 군에서 정강뼈 몸쪽뼈끝부위와 넙다리뼈 먼쪽뼈끝부에 출현한 이차뼈발생중심의 크기는 실험군에서 대조군에 비하여 유의하게 작았다(p⁄0.01). 이차뼈발생중심에 출현한 뼈파괴세포 또는 연골파괴세포 수는 정강뼈와 넙다리뼈 모두에서 alendronate 투여군에서 유의하게 감소되어 있었으며(p⁄0.01), 뼈파괴세포의 평 균 크기는 큰 편차로 인하여 유의한 차이를 보이지 않았다(p¤0.05). 뼈끝연골판의 증식연골세포층 두께는 정강뼈 와 넙다리뼈에서 모두 대조군과 유의한 차이가 없었으나(p¤0.05) 비대연골세포층 두께는 정강뼈와 넙다리뼈 모 두 alendronate 투여에 의하여 유의하게 증가되어 있었다(p⁄0.01). 연골이 흡수되어 뼈로 대치되는 부위, 즉 석회 화 경계면에 출현하는 연골파괴세포 수 또한 alendronate 투여에 의하여 유의하게 감소되었다(p⁄0.01). 이상의 결 과는 bisphosphonate는 연골파괴세포 작용 억제를 통하여 연골 흡수를 억제하는 작용을 가짐을 시사하며, 연골기 질에 미치는 작용 등에 대하여 더 많은 연구가 필요할 것으로 사료된다.
Abstract
Bisphosphonates inhibit bone resorption by affecting osteoclastic function and formation of osteoclasts from their precursor cells. Chondroclasts have the same origin and differentiation as osteoclasts. Thus, it is hypothesized that bisphosphonate can affect on cartilage metabolism. This study was aimed to elucidate effects of alendronate, a nitrogen containing bisphosphonate, on cartilage development in the tibial proximal and femoral distal epiphyseal plates in rats. Alendronate (1 mg/kg) was subcutaneously administered in growing rat pups for 10 days. Several parameters such as the number and size of chondroclasts, involved in cartilage resorption, size of secondary ossification center and thickness of cartilage cell layers were measured and analysed by histomorphometry. The size of the secondary ossification centers in the tibial proximal and femoral distal epiphysis was smaller in the alendronate treated group (p⁄0.01). The number of osteoclasts in the both the ossification centers and chondroclasts beneath the epiphyseal plates was significantly decreased by alendronate treatment (p⁄0.01). The size of chondroclasts was not significantly changed (p¤0.05). The thickness of proliferating cartilage layer was not changed, but by contrast, hypertrophied cartilage layer was increased in thickness by alendronate treatment. These findings suggest that bisphosphonates can affect cartilage cell metabolism in a chondroprotective way.
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