Sanmiao formula inhibits chondrocyte apoptosis and cartilage matrix degradation in a rat model of osteoarthritis
Authors: Zhen-Li Liu
Qian Liu
Ying Xu
Guo-Jing Dai
Na Lin
Zhi-Qian Song
Wei-Heng Chen
Li Li
Journal: Experimental and therapeutic medicine (2014)
Discipline: CLINICAL MEDICINE
Keywords: Sanmiao formula; chondrocytes; collagen; inflammatory cytokines; metalloproteinases
Affiliations: Institutes of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China., Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, P.R. China., Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, P.R. China.

Abstract:  Sanmiao formula (SM) is a basic prescription for the treatment of gouty and rheumatoid arthritis that has been used in China over a long period of history. However, there is no evidence associating SM with the treatment of osteoarthritis (OA). In this study, a characterization of the anti-OA effect of SM was conducted using an in vivo rat model induced by anterior cruciate ligament transection and medial meniscus resection (ACLT plus MMx), together with in vitro studies using chondrocytes for further molecular characterization. Rats subjected to ACLT plus MMx were treated with SM at doses of 0.63, 1.25 and 2.5 g/kg per day for three or six weeks. SM treatment significantly inhibited the histopathological changes of articular cartilage damage and synovial inflammation in the rats following ACLT plus MMx. SM (2.5 g/kg) clearly inhibited chondrocyte apoptosis and prevented cartilage matrix degradation, which was indicated by the increased proteoglycan and collagen content, particularly with regard to type II collagen expression in articular cartilage. Furthermore, SM (2.5 g/kg) markedly inhibited the release of interleukin (IL)-1β, tumor necrosis factor-α and nitric oxide in serum, while simultaneously increasing the levels of bone morphogenetic protein-2 and transforming growth factor-β in the circulation. Notably, SM (2.5 g/kg) clearly attenuated the OA-augmented expression of matrix metalloproteinase (MMP)-13 and augmented the OA-reduced expression of tissue inhibitor of metalloproteinase (TIMP)-1 in the knee joints. In addition, SM significantly reduced the proportion of early and late apoptotic and sub-G1 phase cells, and clearly decreased the expression of MMP-13 and increased that of TIMP-1 at the mRNA and protein levels in IL-1β-induced chondrocytes. These findings provide the first evidence that SM effectively treats OA by inhibiting chondrocyte apoptosis, cartilage matrix degradation and the inflammatory response. 

Retracted: No

PubPeer comments:
 Fig 1:  Effects of SM on cartilage histology and Mankin score in the knee joints of rats following ACLT plus Mmx. Cartilage histology was observed in ACLT plus MMx model and sham-operated rats at the end of a three- or six-week treatment period. Photomicrographs captured at x200 magnification of representative cartilage sections from one animal per treatment group are shown: Sham, untreated ACLT plus MMx (model) and ACLT plus MMx treated with SM at the doses of 0.63, 1.25 and 2.5 g kg (SM).  ![file] Consider e.g. the 6-week 0.63-g kg panel: ![file] , 
 Some additional findings in Figure 1: ![file] , 
 #1  Figure 3. Effects of SM on chondrocyte apoptosis in the knee joints of rats following anterior cruciate ligament transection and medial meniscus resection. ... Photomicrographs were captured at x200 magnification of representative cartilage sections from one animal per group.  ![file] Many visual elements repeat within and between panels. I have only tried to mark a fraction of them. , 
 #2 I was just preparing the image. ![file] ,