title: Neural EGFL-Like 1 Is a Downstream Regulator of Runt-Related Transcription Factor 2 in Chondrogenic Differentiation and Maturation.
abstract: Recent studies indicate that neural EGFL-like 1 (Nell-1), a secretive extracellular matrix molecule, is involved in chondrogenic differentiation. Herein, we demonstrated that Nell-1 serves as a key downstream target of runt-related transcription factor 2 (Runx2), a central regulator of chondrogenesis. Unlike in osteoblast lineage cells where Nell-1 and Runx2 demonstrate mutual regulation, further studies in chondrocytes revealed that Runx2 tightly regulates the expression of Nell-1; however, Nell-1 does not alter the expression of Runx2. More important, Nell-1 administration partially restored Runx2 deficiency-induced impairment of chondrocyte differentiation and maturation in vitro, ex vivo, and in vivo. Mechanistically, although the expression of Nell-1 is highly reliant on Runx2, the prochondrogenic function of Nell-1 persisted in Runx2-/-scenarios. The biopotency of Nell-1 is independent of the nuclear import and DNA binding functions of Runx2 during chondrogenesis. Nell-1 is a key functional mediator of chondrogenesis, thus opening up new possibilities for the application of Nell-1 in cartilage regeneration.
authors.affiliation: Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, California; Department of Orthodontics, Peking University, School and Hospital of Stomatology, Beijing, China.
authors.forename: Chenshuang
authors.initials: C
authors.lastname: Li
authors.affiliation: UCLA Division of Plastic and Reconstructive Surgery, Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Orthodontics, Peking University, School and Hospital of Stomatology, Beijing, China.
authors.forename: Yanheng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
authors.forename: Eric
authors.initials: E
authors.lastname: Chen
authors.affiliation: Oak Ridge National Laboratory, Oak Ridge, Tennessee.
authors.forename: Cymbeline T
authors.initials: CT
authors.lastname: Culiat
authors.affiliation: Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, California; Department of Orthodontics, School of Stomatology, Zhengzhou University, Zhengzhou, China.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, California; Department of Orthodontics, Hospital of Stomatology, Zhejiang University, Hangzhou, China.
authors.forename: Xuepeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, California; UCLA Division of Plastic and Reconstructive Surgery, Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California.
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
authors.affiliation: Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California, Los Angeles, Los Angeles, California. Electronic address: xzhang@dentistry.ucla.edu.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: UCLA Division of Plastic and Reconstructive Surgery, Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California. Electronic address: bsoo@ucla.edu.
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002356:Cartilage / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D019902:Chondrocytes / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology*; D005269:Femur / Q000196:embryology / Q000254:growth & development; D006023:Glycoproteins / Q000502:physiology*; D006614:Hindlimb / Q000502:physiology; D008810:Mice, Inbred C57BL; D012038:Regeneration
chemical_list: D002135:Calcium-Binding Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D006023:Glycoproteins; C513122:Nell1 protein, mouse; C493716:Runx2 protein, mouse