Parking this abstract etc here, as this work is relevant for CARA. I do not want to appear to be a pumper, so caveat emptor. Relevant to the osteoarthritis oral CR845 trial ongoing. JCI is Journal of Clinical Investigation, highly regarded.
Free PDF available at pubmedcentral, follow the abstract link:
ncbi.nlm.nih.gov
JCI Insight. 2017 Jan 12; 2(1): e88553.
Published online 2017 Jan 12. doi: 10.1172/jci.insight.88553
PMCID: PMC5214705
Kappa opioid receptor signaling protects cartilage tissue against posttraumatic degeneration
Ling Wu,1 Shu Zhang,2 Ruzanna Shkhyan,1 Siyoung Lee,1 Francesca Gullo,1 Claire D. Eliasberg,3 Frank A. Petrigliano,3 Kai Ba,2 Jing Wang,4 Yunfeng Lin,2 and Denis Evseenko 1
1Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
2State Key Laboratory for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China.
3Department of Orthopaedic Surgery, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
4Department of Stomatology, Tenth People’s Hospital of Tongji University, Shanghai, China.
Corresponding author.
Ling Wu: ude.csu@uwgnil; Shu Zhang: moc.liamg@uhsgnahz.tsitned; Ruzanna Shkhyan: ude.csu@annazuR; Siyoung Lee: ude.csu@lgnuoyis; Francesca Gullo: moc.liamg@3002ollugacsecnarf; Claire D. Eliasberg: UDE.SSH@cgrebsaile; Kai Ba: moc.nsm@aB.K; Jing Wang: moc.liamtoh@ycart_tsitned; Yunfeng Lin: nc.ude.ucs@nilgnefnuy; Denis Evseenko: ude.csu@okneesve
Address correspondence to: Denis Evseenko, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA. Phone: 1.323.422.2199; E-mail: ude.csu@okneesve. Or to: Yunfeng Lin, State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, 14 South Remin Road 3rd section, Chengdu, China, 610041. Phone: 86.28.85503487; E-mail: nc.ude.ucs@nilgnefnuy.
Abstract
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-a. 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.
From the text:
"In this study, we demonstrate that KOR (kappa opioid receptor, the receptor for CR845) is expressed in human cartilage cells throughout ontogenesis. We also show that KOR stimulation induces secretion of lubricin by chondrocytes and plays both protective and anabolic roles in cartilage tissue. This study demonstrates potentially novel biological functions of KOR outside of the neural system and suggests that this receptor has broader functions than analgesia, mood control, and neuroprotection."
Redlining above done by yours truly. |
