title: Neuroleukin/Autocrine Motility Factor Receptor Pathway Promotes Proliferation of Articular Chondrocytes through Activation of AKT and Smad2/3.
abstract: Cartilage defect is an intractable clinical problem. Therapeutic strategies for cartilage repair are far from optimal due to poor proliferation capacity of chondrocytes. Autologous chondrocyte implantation is a cell based therapy that uses in vitro amplified healthy chondrocytes from the patient. However, chondrocyte dedifferentiation during in vitro culture limits its application. Neuroleukin (NLK) is a multifunctional protein that stimulates cell growth and migration, together with its receptor autocrine motility factor receptor (AMFR, also called gp78). We investigated expression of NLK and AMFR/gp78 during cartilage development in vivo and in cultured articular chondrocytes in vitro, and found the pair associates with chondrocyte proliferation and differentiation. While applied to isolated articular chondrocytes, NLK promotes cell proliferation and secretion of type II collagen, a marker of proliferating chondrocytes. Further work demonstrates that NLK up regulates pAKT and pSmad2/3, but down regulates pSmad1/5. In animals, NLK treatment also promotes chondrocyte proliferation while inhibits terminal differentiation, leading to expanded proliferating zone but decreased prehypertrophic and hypertrophic zones in the growth plate region. NLK is therefore a candidate factor that can be applied in the treatment of cartilage defects.
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Tian
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
authors.forename: Xifu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
authors.forename: Jinrui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
authors.forename: Pixu
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology*; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism*; D015870:Gene Expression; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism*; D006132:Growth Plate / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D060285:Receptors, Autocrine Motility Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*
chemical_list: D051899:Smad2 Protein; D051900:Smad3 Protein; D060285:Receptors, Autocrine Motility Factor; D051057:Proto-Oncogene Proteins c-akt; D005956:Glucose-6-Phosphate Isomerase