Sakao Kei, Takahashi Kenji A, Arai Yuji, Saito Masazumi, Honjyo Kuniaki, Hiraoka Nobuyuki, Kishida Tsunao, Mazda Osam, Imanishi Jiro, Kubo Toshikazu
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
J Orthop Sci. 2009 Nov;14(6):738-47. doi: 10.1007/s00776-009-1401-4. Epub 2009 Dec 8.
To clarify the significance of subchondral bone and osteophytes in the pathology of osteoarthritis (OA), we investigated the expression of asporin (ASPN), transforming growth factor-beta1 (TGF-beta1), TGF-beta2, TGF-beta3, and runt-related transcription factor-2 (Runx2) genes involved in bone metabolism.
Osteoblasts were isolated from 19 patients diagnosed with knee OA and from 4 patients diagnosed with femoral neck fracture. Osteoblast expression of mRNA encoding ASPN, TGF-beta1, TGF-beta2, TGF-beta3, and Runx2 was analyzed using real-time RT-PCR.
Expression of ASPN, TGF-beta1, and TGF-beta3 mRNA in the subchondral bone and osteophytes of OA patients increased compared with that of non-OA patients. The ratio of ASPN to TGF-beta1 mRNA in patients with severe cartilage damage was higher than that in patients with mild cartilage damage.
The increased ratio of ASPN mRNA to TGF-beta1 mRNA in patients with severe relative to mild cartilage damage indicates that increased ASPN mRNA expression was significantly associated with the severity of cartilage degeneration. This finding suggests that ASPN may regulate TGF-beta1-mediated factors in the development of OA, which may provide clues as to the underlying pathology of OA.
为阐明软骨下骨和骨赘在骨关节炎(OA)病理中的意义,我们研究了参与骨代谢的抑瘤素(ASPN)、转化生长因子-β1(TGF-β1)、TGF-β2、TGF-β3和 runt 相关转录因子-2(Runx2)基因的表达。
从19例诊断为膝关节OA的患者和4例诊断为股骨颈骨折的患者中分离成骨细胞。使用实时逆转录聚合酶链反应(RT-PCR)分析编码ASPN、TGF-β1、TGF-β2、TGF-β3和Runx2的mRNA的成骨细胞表达。
与非OA患者相比,OA患者软骨下骨和骨赘中ASPN、TGF-β1和TGF-β3 mRNA的表达增加。严重软骨损伤患者中ASPN与TGF-β1 mRNA的比值高于轻度软骨损伤患者。
严重软骨损伤患者相对于轻度软骨损伤患者,ASPN mRNA与TGF-β1 mRNA的比值增加,表明ASPN mRNA表达增加与软骨退变的严重程度显著相关。这一发现表明,ASPN可能在OA的发展中调节TGF-β1介导的因子,这可能为OA的潜在病理提供线索。