Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model
Authors: Hui B Sun
Mahantesh Navati
David M Hirsh
Zhiyong He
Daniel J Leong
Sun J Kim
Lin Xu
John A Hardin
Joel M Friedman
Neil J Cobelli
Angela Wang
Zhuo Zhang
Journal: Arthritis Research & Therapy (2016)
Discipline: CLINICAL MEDICINE
Keywords: ADAMTS5; Chondroprotection; Curcumin; MMPs; Nutraceuticals
Affiliations: Department of Orthopaedic Surgery, Albert Einstein College of Medicine, Bronx, NY, USA., Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, USA., China-Japan Union Hospital of Jilin University, Bronx, NY, USA., Department of Physiology & Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA., Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA., Department of Orthopaedic Surgery, Albert Einstein College of Medicine, Bronx, NY, USA. ., Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, USA. .

Abstract:  Background: Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM). Methods: Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR. The mice subjected to DMM surgery were orally administered curcumin or topically administered curcumin nanoparticles for 8 weeks. Cartilage integrity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical staining of cleaved aggrecan and type II collagen, and levels of matrix metalloproteinase (MMP)-13 and ADAMTS5. Synovitis and subchondral bone thickness were scored based on histologic images. OA-associated pain and symptoms were evaluated by von Frey assay, and locomotor behavior including distance traveled and rearing. Results: Both curcumin and nanoparticles encapsulating curcumin suppressed mRNA expression of pro-inflammatory mediators IL-1β and TNF-α, MMPs 1, 3, and 13, and aggrecanase ADAMTS5, and upregulated the chondroprotective transcriptional regulator CITED2, in primary cultured chondrocytes in the absence or presence of IL-1β. Oral administration of curcumin significantly reduced OA disease progression, but showed no significant effect on OA pain relief. Curcumin was detected in the infrapatellar fat pad (IPFP) following topical administration of curcumin nanoparticles on the skin of the injured mouse knee. Compared to vehicle-treated controls, topical treatment led to: (1) reduced proteoglycan loss and cartilage erosion and lower OARSI scores, (2) reduced synovitis and subchondral plate thickness, (3) reduced immunochemical staining of type II collagen and aggrecan cleavage epitopes and numbers of chondrocytes positive for MMP-13 and ADAMTS5 in the articular cartilage, and (4) reduced expression of adipokines and pro-inflammatory mediators in the IPFP. In contrast to oral curcumin, topical application of curcumin nanoparticles relieved OA-related pain as indicated by reduced tactile hypersensitivity and improved locomotor behavior. Conclusion: This study provides the first evidence that curcumin significantly slows OA disease progression and exerts a palliative effect in an OA mouse model. 

Retracted: No

PubPeer comments:
 Could the authors please comment on the seemingly repeated area in the upper right corner of an image in Figure 2a? *** ![file] , 
 see ORI research misconduct finding item #8 https: ori.hhs.gov content case-summary-leong-daniel Respondent reused and relabeled photomicrographs from the following published papers to falsely represent unrelated experimental results in NIH grant applications: Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse post-traumatic osteoarthritis model. Arthritis Res Ther. 2014 Dec 17;16(6):508; doi: 10.1186 sl3075-014-0508-y (hereafter referred to as u201cArthritis Res Ther. 2014u201d). note ORI doi is wrong. should be: 10.1186 s13075-014-0508-y [have letter l rather than number 1 ] Erratum in: Arthritis Res Ther. 2019, Jan 3;21(1):1; doi: 10.1186 s13075-018-1791-9. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model. Arthritis Res Ther. 2016 Jun 3; 18(1):128; doi: 10.1186 s13075-016-1025-y (hereafter referred to as u201cArthritis Res Ther. 2016u201d). ,