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Background The relationship between oxytocine (OT) and osteoarthritis (OA) is poorly studied and remains unknown. However the subchondral bone is considered as a major player in osteoarthritis, and a protective effect of OT on bone mineralization is described in recent studies. Objectives The aim of our work was to investigate a possible link between OT and OA Methods we used three different approaches: i) In vitro using MSC (adipose and bone marrow derived stem cells) that were maintained as mono-layer (2D) or as pellets in three dimension (3D) in the absence or the presence of OT. RT-PCR, histological and immunohistochemical analysis were performed. ii) in vivo using a rat animal model developing OA upon anterior cruciate ligament transection (ACLT). Twenty female Wistar rats were divided in 2 groups: one group was sham operated whereas the second was ACL transected. Half of each group received either OT (1 mg/kg/day) injections or saline buffer. Histological analysis was performed on day 28. The severity of OA lesions was assessed on a scale adapted from Mankin9s score at medial part of the femur. iii) Clinical analysis using a human cohort. Samples issued from a hand OA cohort (ADEM). 63 OA women have been included; men were excluded because of their low number. At baseline, all subjects benefited of OT and leptin circulating levels measurements and hand X rays (Scoring systems including Kelgren and Lawrence and Verbruggen scores). The control group consists in subjects of the same age range without osteoporosis, OA or inflammatory disease. Results OT treatment of differentiating MSCs for 21 days induced a significant increase of agrecan, Col X and COMP mRNA levels without variation of Col 1a. Immunostaining experiments showed an improvement of Sox9 and Col II expression in the presence of OT. The histological analysis of rat knee showed no differences in the severity of lesions between the different ACLT groups. The characteristics of the women cohorts is as follow: 63 OA women age = 65 (+/-11), Body Mass Index (BMI) = 24 (+/-4), OT=1.4 (+/-2) and 19 control women age=63 (+/-10), BMI=26 (+/-5), OT=6.5 (+/-7).The multivariate analysis adjusted for age, BMI and leptin levels, showed a significant lower level of OT in hand OA women (p=0.002, β=3.4). In univariate analysis, there was no relationship between OT blood levels and the severity of OA (Verbruggen: p=0.7, KL: p=0.2), Joint Space Narrowing (p=0.2) and osteophytes (p=0.1). Conclusions Our study shows an anabolic effect of OT on chondrogenesis and that OT circulating levels was significantly lower in OA patients. OT might represents an interesting player in the pathophysiology of osteoarthritis and further studies will shed some light on its mechanism of action. Disclosure of Interest None declared |
