Abstract
Both leptin and osteocalcin have been found to affect growth-plate cartilage development through regulation of the physiologic processes of endochondral bone formation. Leptin mediates bone development and osteocalcin secreted in the late stage of osteoblast differentiation. The relationship between leptin and osteocalcin expression in the chondrogenic cells line is still not clear. Thus, the aim of this study was to explore the effect of leptin on the expression of osteocalcin in chondrocytes. We used clonal mouse chondrogenic ATDC5 cells to investigate the relationship between leptin and osteocalcin. We found that both leptin and osteocalcin expression were dynamically expressed during ATDC5 cell differentiation from 4 to 21 days. We also found that leptin significantly upregulated osteocalcin mRNA and protein levels 24 h after leptin stimulation. However, different concentrations and exposure times of osteocalcin did not affect the levels of leptin protein. Furthermore, we confirmed that leptin augmented the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in a time-dependent manner but not p38 or AKT. Inhibition of pERK1/2 expression by a specific ERK1/2 inhibitor U0126 and a special small interfering RNA attenuated levels of leptin-induced osteocalcin expression, indicating that ERK1/2 mediates, in part, the effects of leptin on osteocalcin. Taken together, our results suggest that leptin regulates the expression of osteocalcin in growth plate chondrocytes via the ERK1/2 signaling pathway, while there is no effect on the phosphorylation of either p38 or AKT.
Highlights
The growth and maintenance of the mammalian skeleton is a product of developmental and postnatal processes that occur throughout life
We found that both leptin and osteocalcin expression were dynamically expressed during ATDC5 cell differentiation from 4 to 21 days
Our results suggest that leptin regulates the expression of osteocalcin in growth plate chondrocytes via the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway, while there is no effect on the phosphorylation of either p38 or AKT
Summary
The growth and maintenance of the mammalian skeleton is a product of developmental and postnatal processes that occur throughout life. The growth plate and its primary cell type, the chondrocyte, are integral to endochondral ossification and the linear growth of the long bones [1]. Chondrocytes secrete extracellular matrix molecules characteristic of cartilage, such as collagen type II and X and aggrecan. This process is controlled by many types of endocrine factors, growth factors, thyroid hormone, and leptin [2, 3]. Bone tissue is composed of cells and mineralized extracellular matrix. The latter consists of hydroxyapatite crystals that load a stress-bearing organic matrix of collagen fibers and non-collagenous proteins, such as osteocalcin, osteopontin, osteonectin, and bone sialoproteins. Serum osteocalcin levels are used to evaluate bone metabolism, as a bone formation marker, and it is thought to be a more sensitive marker for bone metabolism than serum alkaline phosphatase activity [6, 7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
