Effect of Ermiao Fang with Xixin (Herba Asari Mandshurici) on bone marrow stem cell directional homing to a focal zone in an osteoarthritis rat model
Authors: Weiheng Chen
Qian Liu
Ying Xu
Guojing Dai
Hongwei Zhu
Na Lin
Tiejun Zhao
Ping Zhang
Journal: Journal of Traditional Chinese Medicine (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Ermiao Fang; Xixin; bone marrow stem cell migration; osteoarthritis; rats

Abstract:  Objective: To investigate the effects of Ermiao Fang (EM) with medical guide Xixin (Herba Asari Mandshurici) (HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis (OA) rats. Methods: OA rats were induced by arthrectomy and assigned to sham-operated, model, EM, or EM plus HAM groups. All rats were injected with recombinant human granulocyte colony-stimulating factor 30 microg x kg(-1) x d(-1) for 7 days and treated with EM or EM plus HAM at 1.6 or 1.9 g x kg(-1) x d(-1) for 3 or 6 weeks, respectively. Chondrocyte apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Levels of interleukin-1 beta (IL-1beta) tumor necrosis factor alpha (TNF-alpha) nitric oxide (NO), and inducible nitric oxide synthase (iNOS) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay. Matrix metalloproteinases (MMPs)-13, tissue inhibitors of metalloproteinases (TIMPs)-1, Bromodeoxyuridine (BrdU), cluster of differentiation 34 (CD34), and stromal cell-derived factor 1 (SDF-1) were measured by immunohistochemical assay. Results: The EM and EM plus HAM groups had significantly less cartilage damage and synovium inflammation the model group. Moreover, the EM and EM plus HAM groups had less chondrocyte apoptosis and more proteoglycan and collagen content than the model group. The EM and EM plus HAM groups had obviously higher MMPs-13 and TIMPs-1 expression in the cartilage than the model group. Moreover, the two formula groups had less release of IL-1beta, TNF-alpha, NO, and iNOS than model group. Importantly, the expressions of BrdU, CD34, and SDF-1 in cartilage were significantly higher in the EM and EM plus HAM-Medtreated rats than model group. Notably, the EM plus HAM treatment seemed to have the greatest effects. Conclusion: HAM improves the therapeutic effects of EM on OA rats by enhancing BMSC directional homing to the focal zone. 

Retracted: No

PubPeer comments:
  Figure 2 Comparison of effects on cartilage histology and Mankin s score A-H: histopathologic changes of cartilage in weeks 3 and 6 (HE staining u00d7200). A-D: histopathologic changes of Sham, Model, EM and EM plus HAM in week 3; E-H: histopathologic changes of Sham, Model, EM and EM plus HAM in week 6. ...Model group: ACLT+MMx without treatment (n=12); sham group: sham operated (n=12); EM group: ACLT+MMx rats treated with EM intragastrically at a daily dose of 1.6 g kg (n=12); EM plus HAM group: ACLT+MMx rats treated with EM (1.6 g kg) plus HAM (0.3 g kg) at a daily dose of 1.9 g kg for 3 or 6 weeks (n=12). ![file] ![file] , 
 Fig 4.  Comparison of effects on chondrocytes apoptosis in weeks 3 and 6A-H: terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining (u00d7200). A-D: the chondrocytes apoptosis of Sham, Model, EM and EM plus HAM in week 3; E-H: The chondrocytes apoptosis of Sham, Model, EM and EM plus HAM at the 6 week ![file] ![file] , 
 Figure 5, C2 and H2 more similar than expected: ![file] , 
 Figure 6 Comparison of expressions of MMP-13 and TIMP-1 in the knee joints (u00d7200)A1-D1: the MMP-13 of Sham, Model, EM and EM plus HAM in week 3; E1-H1: the MMP-13 of Sham, Model, EM and EM plus HAMin week 6. A2-D2: the TIMP-1 of Sham, Model, EM and EM plus HAM in week 3; E2-H2: the TIMP-1 of Sham, Model, EM and EM plusHAM in week 6. Immunohistochemistry was used in all frames. ![file] , 
 #1 There appears to be overlap between the results reported here and the ones in [Xu et al (2014)] . Fig 2: ![] 2A from the companion paper: ![file] , 
 #5 Overall, about 3 4 of the results are the same in the two papers - for Sham operation, Model. EM(R). What differs are the results for EM + HAM here, and EMR + APR in [Xu et al (2014)] . E.g., Fig 5 A3-H3 here, ![file] and Fig 5 Col 2 in the companion paper: ![file] I can imagine that the two experiments were carried out in parallel, then split over two publications, reusing the three control groups in each publication. But was it really necessary to reuse the same representative images, when there were n=12 rats in each group? In addition, one hardly expects to find a cell group present in both the Collagen-II 6-week EM+HAM panel from Fig 5, and Coll-II 6-week EM+APR from the companion Fig 5. ![file] ![file] , 
 An additional finding for Figure 4 from this paper, and a comparison of the Figures 4 from the two papers: * Xu Y et al. Chin J Integr Med 2014, DOI: 10.1007 s11655-014-1761-2 * Xu Y et al. J Tradit Chin Med 2014, DOI: 10.1016 s0254-6272(15)30050-9 (this paper): ![file] , 
 An additional finding in Figure 7, in the CD34 panels of the Sham group, marked in purple (mirror image). The same similarity is also present in its companion figure from the other paper. ![file] ,