title: Leptin Receptor Metabolism Disorder in Primary Chondrocytes from Adolescent Idiopathic Scoliosis Girls.
abstract: To investigate the underlying mechanisms of low metabolic activity of primary chondrocytes obtained from girls with adolescent idiopathic scoliosis (AIS); AIS is a spine-deforming disease that often occurs in girls. AIS is associated with a lower bone mass than that of healthy individuals and osteopenia. Leptin was shown to play an important role in bone growth. It can also regulate the function of chondrocytes. Changes in leptin and Ob-R levels in AIS patients have been reported in several studies. The underlying mechanisms between the dysfunction of peripheral leptin signaling and abnormal chondrocytes remain unclear; The following parameters were evaluated in AIS patients and the control groups: total serum leptin levels; Ob-R expression in the plasma membrane of primary chondrocytes; JAK2 and STAT3 phosphorylation status. Then, we inhibited the lysosome and proteasome and knocked down clathrin heavy chain (CHC) expression in primary chondrocytes isolated from girls with AIS and evaluated Ob-R expression. We investigated the effects of leptin combined with a lysosome inhibitor or CHC knockdown in primary chondrocytes obtained from AIS patients; Compared with the controls, AIS patients showed similar total serum leptin levels, reduced JAK2 and STAT3 phosphorylation, and decreased cartilage matrix synthesis in the facet joint. Lower metabolic activity and lower membrane expression of Ob-R were observed in primary chondrocytes from the AIS group than in the controls. Lysosome inhibition increased the total Ob-R content but had no effect on the membrane expression of Ob-R or leptin's effects on AIS primary chondrocytes. CHC knockdown upregulated the membrane Ob-R levels and enhanced leptin's effects on AIS primary chondrocytes; The underlying mechanism of chondrocytes that are hyposensitive to leptin in some girls with AIS is low plasma membrane Ob-R expression that results from an imbalance between the rate of receptor endocytosis and the insertion of newly synthesized receptors into the membrane.
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, China. philar1213@csu.edu.cn.
authors.forename: Yun-Jia
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, China. hixiatiantian@126.com.
authors.forename: Hong-Gui
authors.initials: HG
authors.lastname: Yu
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, China. Dreamcastlove@126.com.
authors.forename: Zhen-Hai
authors.initials: ZH
authors.lastname: Zhou
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, China. guoyisen1207@126.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, China. wlj2096@163.com.
authors.forename: Long-Jie
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, China. zhq9996@163.com.
authors.forename: Hong-Qi
authors.initials: HQ
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008659:Metabolic Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D012600:Scoliosis / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D020738:Leptin; D054411:Receptors, Leptin
keywords: Ob-R; adolescent idiopathic scoliosis; leptin; pathogenesis