Petersson M, Bucht E, Granberg B, Stark A
Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Institutet and Karolinska University Hospital, S-171 76 Stockholm, Sweden.
Osteoarthritis Cartilage. 2006 Jul;14(7):652-9. doi: 10.1016/j.joca.2006.01.003. Epub 2006 Feb 17.
Both arg-vasopressin (AVP) and parathyroid hormone-related protein (PTHrP) may act as proinflammatory hormones. In addition, they have been suggested to be involved in the pathophysiology of rheumatoid arthritis (RA). We therefore investigated the effects of AVP and PTHrP (1-34) on cell proliferation and secretion of the glycoprotein YKL-40 in human chondrocytes derived from healthy subjects as well as from patients with RA or osteoarthritis (OA).
Primary cultures of human chondrocytes were incubated with AVP (1-100 pmol/l) or PTHrP (1-34) (0.1-100 nmol/l). Cell proliferation was measured as [3H]thymidine incorporation. Intracellular cAMP and YKL-40 in cell medium were determined by commercially available kits.
AVP and PTHrP (1-34) increased proliferation in chondrocytes derived from healthy donors as well as from RA and OA patients. PTHrP (1-34), but not AVP, increased intracellular levels of cAMP. PTHrP (1-34) did not change the amount of YKL-40 in chondrocytes from healthy subjects or patients with OA. AVP tended to decrease the secretion of YKL-40 from healthy chondrocytes. Both PTHrP (1-34) and AVP increased YKL-40 secretion from RA chondrocytes. In contrast, AVP decreased the secretion of YKL-40 in chondrocytes from patients with OA.
AVP and PTHrP (1-34) stimulated proliferation in human chondrocytes derived from healthy subjects as well as from patients with RA or OA. However, the effects of AVP and PTHrP (1-34) on YKL-40 secretion varied depending on the origin of the chondrocytes.
精氨酸加压素(AVP)和甲状旁腺激素相关蛋白(PTHrP)都可能作为促炎激素。此外,它们被认为参与了类风湿关节炎(RA)的病理生理过程。因此,我们研究了AVP和PTHrP(1-34)对来自健康受试者以及RA或骨关节炎(OA)患者的人软骨细胞增殖和糖蛋白YKL-40分泌的影响。
将人软骨细胞原代培养物与AVP(1-100 pmol/l)或PTHrP(1-34)(0.1-100 nmol/l)一起孵育。通过[3H]胸苷掺入法测量细胞增殖。使用市售试剂盒测定细胞培养基中的细胞内cAMP和YKL-40。
AVP和PTHrP(1-34)增加了来自健康供体以及RA和OA患者的软骨细胞的增殖。PTHrP(1-34)而非AVP增加了细胞内cAMP水平。PTHrP(1-34)未改变健康受试者或OA患者软骨细胞中YKL-40的量。AVP倾向于减少健康软骨细胞中YKL-40的分泌。PTHrP(1-34)和AVP均增加了RA软骨细胞中YKL-40的分泌。相反,AVP减少了OA患者软骨细胞中YKL-40的分泌。
AVP和PTHrP(1-34)刺激了来自健康受试者以及RA或OA患者的人软骨细胞的增殖。然而,AVP和PTHrP(1-34)对YKL-40分泌的影响因软骨细胞的来源而异。