Nervous System Stem Cells Research Center , Semnan University of Medical Sciences, Semnan, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Ir J Med Sci. 2023 Jun;192(3):1191-1196. doi: 10.1007/s11845-022-03061-3. Epub 2022 Jun 24.
Evidence has shown that cysteine protease enzymes, such as cathepsin D, cathepsin A, cathepsin K, and alpha-1 antitrypsin (AAT) are involved in the chronic degenerative joint process. This study aimed to determine the potential involvement of cathepsin K, cathepsin D, and AAT in patients with osteoarthritis (OA).
This study was performed on 31 patients with knee OA and 29 age- and sex-matched healthy subjects (both with Fars ethnicity from Iran). American College of Rheumatology (ACR) criteria were used to diagnose OA patients. The clinical status of the patients was scored by Western Ontario McMaster Universities Osteoarthritis (WOMAC), and pain intensity was measured by the Visual Analog Scale (VAS). The serum level of AAT was measured using high-resolution cellulose acetate electrophoresis. Additionally, serum levels of cathepsin D and cathepsin K were measured by enzyme-linked immunosorbent assay (ELISA).
The findings showed that the serum level of cathepsin K was significantly increased in OA patients compared to healthy subjects (P = 0.01), while there was no significant difference between serum level of cathepsin D in study groups (P = 0.2). In addition, the serum concentration of AAT was significantly decreased in OA patients compared to healthy subjects (P = 0.003). There was a significant correlation between WOMAC score and age (r = 0.644, P = 0.0001) and VAS (r = 0.866, P < 0.0001) in OA patients.
The decreased level of AAT in OA patients and a rise in serum level of cathepsin K are involved in the pathogenesis of OA via stimulation of bone resorption and cartilage degradation.
有证据表明,半胱氨酸蛋白酶酶,如组织蛋白酶 D、组织蛋白酶 A、组织蛋白酶 K 和α-1 抗胰蛋白酶 (AAT),参与慢性退行性关节过程。本研究旨在确定组织蛋白酶 K、组织蛋白酶 D 和 AAT 与骨关节炎 (OA) 患者的潜在相关性。
本研究纳入 31 名膝关节 OA 患者和 29 名年龄和性别匹配的健康对照者(均来自伊朗的法尔斯族裔)。采用美国风湿病学会 (ACR) 标准诊断 OA 患者。采用 Western Ontario McMaster Universities Osteoarthritis (WOMAC) 对患者的临床状况进行评分,采用视觉模拟量表 (VAS) 测量疼痛强度。采用高分辨率醋酸纤维素电泳法测定 AAT 的血清水平。此外,采用酶联免疫吸附试验 (ELISA) 测定组织蛋白酶 D 和组织蛋白酶 K 的血清水平。
结果显示,OA 患者的组织蛋白酶 K 血清水平明显高于健康对照组(P=0.01),而两组间组织蛋白酶 D 血清水平无显著差异(P=0.2)。此外,OA 患者的 AAT 血清浓度明显低于健康对照组(P=0.003)。OA 患者的 WOMAC 评分与年龄呈显著正相关(r=0.644,P=0.0001),与 VAS 评分呈显著正相关(r=0.866,P<0.0001)。
OA 患者 AAT 水平降低,组织蛋白酶 K 血清水平升高,通过刺激骨吸收和软骨降解,参与 OA 的发病机制。