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.
Highlights
Adolescent idiopathic scoliosis (AIS) is a spine-deforming disease with an approximately 5% incidence rate [1]
Human facet joints were obtained from the AIS and the control group during surgery, and primary chondrocytes were isolated from the cartilage tissue
Adolescent idiopathic scoliosis is a spine-deforming disease characterized by three-dimensional deformation of the spine and an approximately 5% incidence rate
Summary
Adolescent idiopathic scoliosis (AIS) is a spine-deforming disease with an approximately 5% incidence rate [1]. Several theories on the etiology of AIS strongly suggest that the occurrence of AIS might involve hormonal, metabolic, neuromuscular, growth-related, and genetic abnormalities [2]. One theory is that scoliosis mainly results from relative anterior spinal over-growth (RASO) with uncoupled neuro-osseous growth [3]. Previous studies have shown overgrowth of the spinal anterior vertebral column with a relatively short spinal cord [4]. Low body weights, low body mass indexes (BMI), low bone masses, and osteopenia have been documented in AIS patients [5,6], which may correlate with growth factor disturbances. AIS might be a systemic disease, and scoliosis is one of the abnormal growth patterns
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