Objective

Retinol binding protein 4 (RBP4) is a member of the lipocalin family and a vitamin A carrier in the blood. More recently, RBP4 has been described as an adipokine that is involved in insulin resistance and metabolic syndrome (MetS). As obesity, MetS and some adipokines contribute to the pathogenesis of osteoarthritis (OA), we investigated RBP4 in patients with OA.

Materials and methods

Cartilage, synovial fluid and blood samples were collected from 100 OA patients undergoing total knee replacement surgery. Primary chondrocytes and cartilage tissue were cultured to measure the RBP4 expression. The concentrations of RBP4, other adipokines (adipsin, adiponectin, leptin and resistin) and biomarkers of OA (COMP, MMP-1, MMP-3 and YKL-40) were measured by immunoassay, and gene expression was measured by next-generation RNA sequencing.

Results

The OA cartilage samples released RBP4 into the culture medium, and the levels correlated positively with the expression of the adipokines adipsin, adiponectin, leptin and resistin. RBP4 was the most prominently expressed of these adipokines in the OA chondrocytes, and the expression of the RBP4 receptors STRA6 (stimulated by retinoic acid gene homologue 6) and TLR4 (Toll-like receptor 4) was also detected. Within the cartilage culture medium, RBP4 showed a positive correlation with MMP-1, MMP-3 and YKL-40. RBP4 was also present in the synovial fluid from the OA patients and correlated positively with the concentrations of RBP4 found in the plasma and the cartilage culture medium. Plasma RBP4 concentrations also showed a positive correlation with MMP-3 and adipsin.

Conclusions

We show here, for the first time, that RBP4 is produced within OA joints and that it is associated with increased levels of adipokines and MMPs. The results suggest a role for RBP4 in the pathogenesis of OA and as a possible target for the disease-modifying drugs for the treatment of OA.

中文翻译：

---

与OA有关的新型脂肪因子：视黄醇结合蛋白4（RBP4）是由软骨产生的，并与骨关节炎患者的MMPs相关。

目的

视黄醇结合蛋白4（RBP4）是脂环蛋白家族的成员，并且是血液中的维生素A载体。最近，RBP4被描述为与胰岛素抵抗和代谢综合征（MetS）有关的脂肪因子。由于肥胖，MetS和某些脂肪因子与骨关节炎（OA）的发病机理有关，因此我们研究了OA患者的RBP4。

材料和方法

从接受全膝关节置换手术的100例OA患者中收集软骨，滑液和血液样本。培养原代软骨细胞和软骨组织以测量RBP4表达。通过免疫测定法测定OA的RBP4，其他脂联素（脂溶素，脂联素，瘦素和抵抗素）和OA的生物标志物（COMP，MMP-1，MMP-3和YKL-40）的浓度，并用下一代RNA测定基因表达排序。

结果

OA软骨样品将RBP4释放到培养基中，其水平与脂联素adipsin，脂联素，瘦素和抵抗素的表达呈正相关。RBP4是这些脂肪因子在OA软骨细胞中最突出的表达，并且还检测到RBP4受体STRA6（受视黄酸基因同源物6刺激）和TLR4（Toll样受体4）的表达。在软骨培养基中，RBP4与MMP-1，MMP-3和YKL-40呈正相关。RBP4也存在于OA患者的滑液中，并与血浆和软骨培养基中的RBP4浓度呈正相关。血浆RBP4浓度也与MMP-3和adipsin呈正相关。

结论

我们首次在这里表明，RBP4是在OA关节内产生的，并且与脂肪因子和MMP的水平升高有关。结果表明RBP4在OA的发病机理中的作用，并可能作为治疗OA的疾病改良药物的靶标。