title: Effect of Ermiao Recipe with medicinal guide Angelicae Pubescentis Radix on promoting the homing of bone marrow stem cells to treat cartilage damage in osteoarthritis rats.
abstract: OBJECTIVE
  To investigate the effect of Ermiao Recipe (, EMR) with medicinal guide Angelicae Pubescentis Radix (APR) on the homing of bone marrow stem cells (BMSCs) to focal zone in osteoarthritis (OA) rats.
  
  
  METHODS
  Forty-eight Sprague-Dawley rats were randomly assigned to the sham-operated, model, EMR, and EMR plus APR groups (12 rats in each group). The OA rat model was induced by anterior cruciate ligament transection and medial meniscus resection. All rats were injected with recombinant human granulocyte colonystimulating factor [rhG-CSF, 30 μg/(kg·d) for continuous 7 days], and rats in the EMR and EMR plus APR groups were treated with EMR or EMR plus APR at 1.6 or 1.9 g/(kg·d) for 3 or 6 weeks, respectively. Cartilage histopathologic changes were observed by hematoxylin and eosin staining. Chondrocytes apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Interleukin-1β (IL-1 β), tumor necrosis factor α (TNF-α), bone morphogenetic protein 2 (BMP-2), and transforming growth factor beta-1 (TGF-β1) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay assay. Matrix metalloproteinase (MMP)-13, tissue inhibitors of metalloproteinase (TIMP)-1, bromodeoxyuridine (BrdU), cluster of differentiation 34 (CD34), and stromal cell derived factor 1 (SDF-1) were measured by immunohistochemistry assay.
  
  
  RESULTS
  EMR and EMR plus APR significantly inhibited articular cartilage damage and synovium inflammation in OA rats at 3 or 6 weeks of treatment, the most obvious changes in these parameters were found in the EMR plus APR group. At 6 weeks, compared with EMR treatment, EMR plus APR remarkably inhibited chondrocytes apoptosis and the release of IL-1β and TNF-α, obviously decreased MMP-13 expression, and significantly increased expressions of proteoglycan, collagen, type II collagen and TIMP-1, serum levels of BMP-2 and TGF-β1 as well as expressions of BrdU, CD34 and SDF-1 in cartilage articular (P<0.01 or P<0.05).
  
  
  CONCLUSIONS
  The medicinal guide APR improved the therapeutic effects of EMR on OA rats by promoting directional homing of BMSCs to focal zone.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Guo-jing
authors.initials: GJ
authors.lastname: Dai
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Wei-heng
authors.initials: WH
authors.lastname: Chen
authors.forename: Na
authors.initials: N
authors.lastname: Lin
mesh_terms: D029969:Angelica; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2 / Q000097:blood; D001973:Bromodeoxyuridine / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D010003:Osteoarthritis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D055396:Bone Morphogenetic Protein 2; D054377:Chemokine CXCL12; D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C000596356:ermiao; D016179:Granulocyte Colony-Stimulating Factor; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D053509:Matrix Metalloproteinase 13; D001973:Bromodeoxyuridine; C000595205:duhuo
references.citation: N Engl J Med. 1994 Oct 6;331(14):889-95
references.pmid: 8078550
references.citation: Bone. 2006 Feb;38(2):234-43
references.pmid: 16185945
references.citation: J Orthop Res. 2001 Sep;19(5):785-96
references.pmid: 11562122
references.citation: Clin Orthop Relat Res. 2000 May;(374):212-34
references.pmid: 10818982
references.citation: Osteoarthritis Cartilage. 2009 Aug;17(8):971-9
references.pmid: 19303469
references.citation: Arthritis Rheum. 2000 Nov;43(11):2563-70
references.pmid: 11083281
references.citation: Arthritis Rheum. 2002 Aug;46(8):1986-96
references.pmid: 12209500
references.citation: Stem Cell Res Ther. 2012 Jul 09;3(4):25
references.pmid: 22776206
references.citation: Osteoarthritis Cartilage. 2013 Feb;21(2):385-393
references.pmid: 23186943
references.citation: Chin J Integr Med. 2013 Jun;19(6):459-63
references.pmid: 22528754
references.citation: Cell Death Differ. 2008 Jan;15(1):143-51
references.pmid: 17962815
references.citation: Arthritis Rheum. 2004 Apr;50(4):1193-206
references.pmid: 15077302
references.citation: Science. 2000 Nov 24;290(5496):1479-81
references.pmid: 11185499
references.citation: Curr Opin Rheumatol. 2004 Sep;16(5):599-603
references.pmid: 15314501
references.citation: Blood. 2001 Jun 1;97(11):3354-60
references.pmid: 11369624
references.citation: Clin Orthop Relat Res. 1994 Jan;(298):296-304
references.pmid: 8118990
references.citation: J Orthop Res. 2010 Mar;28(3):361-9
references.pmid: 19810106
references.citation: Expert Opin Biol Ther. 2009 Nov;9(11):1399-405
references.pmid: 19793003
references.citation: J Bone Joint Surg Am. 1971 Apr;53(3):523-37
references.pmid: 5580011
references.citation: Blood. 1996 Jan 1;87(1):1-13
references.pmid: 8547630
references.citation: Birth Defects Res C Embryo Today. 2003 Aug;69(3):250-6
references.pmid: 14671778
references.citation: Chin J Integr Med. 2012 Oct;18(10):761-8
references.pmid: 22241502
references.citation: Biorheology. 2002;39(1-2):237-46
references.pmid: 12082286
references.citation: Biochem Biophys Res Commun. 2005 May 13;330(3):633-40
references.pmid: 15809044
references.citation: Nat Rev Rheumatol. 2011 Jan;7(1):33-42
references.pmid: 21119608
references.citation: Biochem Biophys Res Commun. 2004 Jul 30;320(3):914-9
references.pmid: 15240135
references.citation: Arthritis Res. 2002;4(1):30-5
references.pmid: 11879535
references.citation: Int J Mol Med. 2012 Apr;29(4):619-24
references.pmid: 22294024