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.

Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis

“…Then, the remaining 36 articles were read through, and 25 were unqualified due to inappropriate study or incomplete data for systematic review. Eventually, 9 studies were qualified for this meta-analysis [ 11 , 12 , 17 – 22 ]. QUADAS-2 quality assessment for the included studies is shown in Fig.…”

“…The extracted information from each paper, including first author, year of publication, number of cases and controls, and mean levels of leptin and ghrelin, is shown in Table 1 . Among these included 9 articles, 6 articles explored changes of serum leptin and sOB-R in AIS [ 11 , 12 , 17 – 19 ], another 2 explored changes of ghrelin in AIS [ 21 , 22 ], while the remaining one study both leptin and ghrelin in AIS [ 20 ]. A total of 700 AIS patients and 3536 healthy controls were included for the meta-analysis of leptin, while 198 AIS patients and 138 healthy controls were included for ghrelin analysis.…”

High Ghrelin Level Predicts the Curve Progression of Adolescent Idiopathic Scoliosis Girls

“…Leptin and ghrelin antagonize each other in regulating energy balance [ 14 ]. A number of studies have reported serum leptin and ghrelin level disorders in AIS patients [ 15 – 20 ]. However, the significance of leptin or ghrelin as a biomarker in progressive AIS patients has not yet been reported.…”

Dexamethasone Down-regulates Osteocalcin in Bone Cells through Leptin Pathway

“…It binds to the leptin receptor (Ob-R) which is expressed as several different isoforms 8 . Leptins and leptin receptors have now been shown to be expressed in a number of organs and tissues in addition to adipose tissue 9 , 10 . Leptins have diverse effects on bone tissue regulation with leptin receptor mutations 11 .…”