The role of neuropeptide on the bone metabolism

关节炎通常伴有骨破坏，这是由滑膜与骨连接处的破骨细胞引起的。本研究旨在探讨神经肽P物质（SP）对滑膜成纤维细胞形成破骨细胞的影响。大鼠膝关节滑膜成纤维细胞表达SP受体、神经激肽1受体（NK，-R）。加入SP可促进滑膜成纤维细胞的增殖，这种作用可被SP或NK_1、-R拮抗剂所抑制。通过逆转录-聚合酶链反应和免疫荧光染色证实，加入SP后，滑膜成纤维细胞中核因子κ B配体受体激活剂（RANKL）的表达增加。滑膜成纤维细胞中骨保护素的表达与SP孵育后下降。在滑膜成纤维细胞和大鼠外周血单核细胞的共培养物中，SP刺激破骨细胞生成。这些结果表明，关节腔中的SP可能通过增加滑膜中RANKL的表达引起滑膜肥大和诱导破骨细胞形成增加。

Arthritis is often accompanied by the destruction of bone, which is caused by osteoclasts at the attachment of the synovium to bone. This study was designed to evaluate the effects of neuropeptide substance P (SP) on the formation of osteoclasts via synovial fibroblastic cells. Synovial fibroblastic cells derived from rat knee joint expressed the SP receptor; neurokinin-1 receptor (NK,-R). The addition of SP stimulated the proliferation of synovial fibroblastic cells and this effect was inhibited by SP or NK_1,-R antagonists. Increased expression of the receptor activator of nuclear factor kappaB ligand (RANKL) in synovial fibroblastic cells after the addition of SP was demonstrated by reverse transcriptase-polymerase chain reaction and immunofluorescence staining. Osteoprotegerin expression in synovial fibroblastic cells was decreased after incubation with SP. In co-cultures of synovial fibroblastic cells and rat peripheral blood monocytes, SP stimulated osteoclastogenesis. These results suggest that SP in the joint cavity may cause both hypertrophy of the synovium and induction of increased osteoclast formation through the increased expression of RANKL in the synovium.