Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
State Key Laboratory for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China.
JCI Insight. 2017 Jan 12;2(1):e88553. doi: 10.1172/jci.insight.88553.
Osteoarthritis is the most common form of arthritis, and pain relief with opioid-like drugs is a commonly used therapeutic for osteoarthritic patients. Recent studies published by our group showed that the kappa opioid receptor (KOR) is highly expressed during human development in joint-forming cells. However, the precise role of this receptor in the skeletal system remains elusive. The main aim of the current study was to investigate the role of KOR signaling in synovial and cartilaginous tissues in pathological conditions. Our data demonstrate that KOR null mice exhibit accelerated cartilage degeneration after injury when compared with WT mice. Activation of KOR signaling increased the expression of anabolic enzymes and inhibited cartilage catabolism and degeneration in response to proinflammatory cytokines such as TNF-α. In addition, selective KOR agonists increased joint lubrication via the activation of cAMP/CREB signaling in chondrocytes and synovial cells. Taken together, these results demonstrate direct effects of KOR agonists on cartilage and synovial cells and reveals a protective effect of KOR signaling against cartilage degeneration after injury. In addition to pain control, local administration of dynorphin or other KOR agonist represents an attractive therapeutic approach in patients with early stages of osteoarthritis.
骨关节炎是最常见的关节炎形式，阿片样药物缓解疼痛是骨关节炎患者常用的治疗方法。我们小组最近发表的研究表明，κ 阿片受体（KOR）在人类发育过程中关节形成细胞中高度表达。然而，该受体在骨骼系统中的确切作用仍不清楚。本研究的主要目的是研究 KOR 信号在滑膜和软骨组织中的作用在病理条件下。我们的数据表明，与 WT 小鼠相比，KOR 缺失小鼠在损伤后软骨退化加速。KOR 信号的激活增加了合成酶的表达，并抑制了软骨的分解代谢和退变对促炎细胞因子如 TNF-α的反应。此外，选择性 KOR 激动剂通过激活软骨细胞和滑膜细胞中的 cAMP/CREB 信号增加关节润滑。总之，这些结果表明 KOR 激动剂对软骨和滑膜细胞有直接作用，并揭示了 KOR 信号对损伤后软骨退化的保护作用。除了控制疼痛外，局部给予 dynorphin 或其他 KOR 激动剂代表了治疗早期骨关节炎患者的一种有吸引力的治疗方法。
