title: CXC chemokine ligand 12a enhances chondrocyte proliferation and maturation during endochondral bone formation.
abstract: OBJECTIVE
  We investigated the roles of CXC chemokine ligand 12a (CXCL12a), also known as stromal cell-derived factor-1α (SDF-1α), in endochondral bone growth, which can give us important clues to understand the role of CXCL12a in osteoarthritis (OA).
  
  
  METHODS
  Primary chondrocytes and tibial explants from embryonic 15.5 day-old mice were cultured with recombinant mouse CXCL12a. To assess the role of CXCL12a in chondrogenic differentiation, we conducted mesenchymal cell micromass culture.
  
  
  RESULTS
  In tibia organ cultures, CXCL12a increased total bone length in a dose-dependent manner through proportional effects on cartilage and bone. In accordance with increased length, CXCL12a increased the protein level of proliferation markers, such as cyclin D1 and proliferating cell nuclear antigen (PCNA), in primary chondrocytes as well as in tibia organ culture. In addition, CXCL12a increased the expression of Runx2, Col10 and MMP13 in primary chondrocytes and tibia organ culture system, implying a role of CXCL12a in chondrocyte maturation. Micromass cultures of limb-bud mesenchymal progenitor cells (MPCs) revealed that CXCL12a has a limited effect on early chondrogenesis, but significantly promoted maturation of chondrocytes. CXCL12a induced the phosphorylation of p38 and Erk1/2 MAP kinases and IκB. The increased expression of cyclin D1 by CXCL12a was significantly attenuated by inhibitors of MEK1 and NF-κB. On the other hand, p38 and Erk1/2 MAP kinase and NF-κB signaling were associated with CXCL12a-induced expression of Runx2 and MMP13, the marker of chondrocyte maturation.
  
  
  CONCLUSIONS
  CXCL12a promoted the proliferation and maturation of chondrocytes, which strongly suggest that CXCL12a may have a negative effect on articular cartilage and contribute to OA progression.
authors: Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital, Daegu, South Korea; Division of Rheumatology, Department of Internal Medicine, Daegu Fatima Hospital, Daegu, South Korea. Electronic address: drgunwoo@gmail.com.
authors: G-W
authors: GW
authors: Kim
authors: Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital, Daegu, South Korea.
authors: M-S
authors: MS
authors: Han
authors: Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital, Daegu, South Korea. Electronic address: 85hrpark@naver.com.
authors: H-R
authors: HR
authors: Park
authors: Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital, Daegu, South Korea. Electronic address: cord2007@hanmail.net.
authors: E-J
authors: EJ
authors: Lee
authors: Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital, Daegu, South Korea. Electronic address: jungykwan@gmail.com.
authors: Y-K
authors: YK
authors: Jung
authors: Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada. Electronic address: susmani@uwo.ca.
authors: S E
authors: SE
authors: Usmani
authors: Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada. Electronic address: vulici@uwo.ca.
authors: V
authors: V
authors: Ulici
authors: Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital, Daegu, South Korea; Division of Rheumatology, Department of Internal Medicine, Daegu Fatima Hospital, Daegu, South Korea. Electronic address: kiefe73@gmail.com.
authors: S-W
authors: SW
authors: Han
authors: Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada. Electronic address: fbeier@uwo.ca.
authors: F
authors: F
authors: Beier
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects*; D020219:Chondrogenesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051379:Mice; D009924:Organ Culture Techniques; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013977:Tibia / Q000187:drug effects / Q000254:growth & development
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D011994:Recombinant Proteins
keywords: CXC motif chemokine 12a; Chondrocyte; Maturation; Osteoarthritis; Proliferation