본 연구에서는 HPL-04가 골관절염의 예방 및 치료 약물로서의 가능성을 탐색하여 다음과 같은 결론을 얻었다. HPL-04는 연골세포 생존율과 연골형성과 관련된 collagen type II, SOX 9 그리고 aggrecan의 유전자 발현을 유의성 있게 증가시킬 뿐만 아니라 염증성 인자와 관련 있는 MMP-2, 9도 유의성 있게 감소시켰다. HPL-04는 MIA에 의해 유도된 퇴행성 골관절염에서 관절연골의 파괴와 골 침식 등 연골의 변성을 억제했으며 proteoglycan의 소실을 유의성 있게 감소시켰다. 이에 본 연구는 HPL-04가 부작용이 적고 약리효과가 뛰어나 골관절염 예방 및 치료제 개발에 활용될 수 있을 것으로 본다.
HanPoong Leading (HPL)-04 were prepared with different oriental medicines (balk of Kalopanax pictus balk, Chaenomelis Fructus, Angelica gigas root, Zingiber officinale, Raphanus sativus Linne and Saururus chinensis Baill.) to investigate the protective effects of HPL-04 on cartilage degradation in knee osteoarthritis (OA). Rat articular chondrocytes incubated with rhIL-$1{alpha}$ markedly increased matrix metalloproteinase (MMP)-2 and 9 activities, decreased cell viability and reduced chondrogenic gene expression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, MMP-2 and 9 activities and real time RT-PCR indicated that HPL-04 counteracted these harmful effects in dose-dependent manner. In addition, for experimental OA in vivo, monosodium iodoacetate (MIA, 0.5 mg/50 ${mu}L$) was injected into knee joints of rats and administered HPL-04 to rats for 4 consecutive weeks after MIA treatment. The experimental data showed that treatment with HPL-04 significantly prevented of MMP-2 and 9 activities in articular cartilage. Histopathological and micro-CT evaluations of the knee joints also revealed that HPL-04 effectively ameliorated MIA-induced degenerative OA. In conclusion, HPL-04 has potential applicability for the prevention and treatment of degenerative OA.
