title: Col2-Cre and tamoxifen-inducible Col2-CreER target different cell populations in the knee joint.
abstract: OBJECTIVE
  Collagen type 2 (Col2)-Cre or tamoxifen-inducible Col2-CreER transgenic mouse lines have been used for studies to explore the cellular and molecular pathogenesis of osteoarthritis (OA). The purpose of this study is to investigate whether the targeted cells are the same or different in the two mouse lines.
  
  
  METHODS
  We crossed tamoxifen inducible Col2-CreER and Col2-Cre mice with Rosa tdTomato reporter mice and analyzed the labeling patterns at different time points.
  
  
  RESULTS
  In the Col2-CreER mice, 90.8 [95% confidence interval (CI) (88.3, 93.2)] and 82.8 (77.4, 88.3) % of the articular surface cells are Tomato positive when tamoxifen was administered at 2 and 2.5 weeks of age and strong activity was observed even 4.5 months after injection. However, 46.0 (32.8, 59.1) and 22.2 (11.7, 32.6) % of the surface cells were Tomato positive when tamoxifen was administered at 3 and 4 weeks of age, respectively. Little to no Tomato activity in the articular surface cells was observed when tamoxifen was administered at 8 weeks of age. At any stage of tamoxifen injection, the Tomato activity was detected in growth plate and epiphyseal bone in addition to articular chondrocytes, but little in endosteum and not in the synovium and ligament. In contrast, the targeted tissues in the Col2-Cre mouse line were articular cartilage, growth plate, meniscus, endosteum, ligament, bone and synovium.
  
  
  CONCLUSIONS
  This study demonstrates that the pattern of targeted cells in the inducible Col2-CreER mice are partially overlapping with but different from that of targeted cells in Col2-Cre mice and the pattern varies dependent on when tamoxifen is administered.
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA. Electronic address: Masashi_Nagao@hsdm.harvard.edu.
authors.forename: M
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Cheong
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA. Electronic address: bjorn_olsen@hms.harvard.edu.
authors.forename: B R
authors.initials: BR
authors.lastname: Olsen
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D017930:Genes, Reporter; D006132:Growth Plate / Q000378:metabolism*; D007719:Knee Joint / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D013264:Stifle / Q000378:metabolism*; D013629:Tamoxifen
chemical_list: D024043:Collagen Type II; D008164:Luminescent Proteins; D013629:Tamoxifen
keywords: Col2-Cre; Col2-CreER; Osteoarthritis; Tamoxifen