Abnormal osteogenic and chondrogenic differentiation of human mesenchymal stem cells from patients with adolescent idiopathic scoliosis in response to melatonin.
Abnormalities of membranous and endochondral ossification in patients with adolescent idiopathic scoliosis (AIS) remain incompletely understood. To investigate abnormalities in the melatonin signaling pathway and cellular response to melatonin in AIS, a case‑control study of osteogenic and chondrogenic differentiation was performed using human mesenchymal stem cells (hMSCs). AIS was diagnosed by physical and radiographic examination. hMSCs were isolated from the bone marrow of patients with AIS and control subjects (n=12 each), and purified by density gradient centrifugation. The expression levels of melatonin receptors (MTs) 1 and 2 were detected by western blotting. Osteogenic and chondrogenic differentiation was induced by culturing hMSCs in osteogenic and chondrogenic media containing vehicle or 50 nM melatonin. Alkaline phosphatase (ALP) activity assays, quantitative glycosaminoglycan (GAG) analysis, and reverse transcription‑quantitative polymerase chain reaction analysis were performed. Compared with controls, MT2 demonstrated low expression in the AIS group. Melatonin increased ALP activity, GAG synthesis and upregulated the expression of genes involved in osteogenic and chondrogenic differentiation including, ALP, osteopontin, osteocalcin, runt-related transcription factor 2, collagen type II, collagen type X, aggrecan and sex‑determining region Y-box 9 in the normal control hMSCs, but did not affect the AIS groups. Thus, AIS hMSCs exhibit abnormal cellular responses to melatonin during osteogenic and chondrogenic differentiation, which may be associated with abnormal membranous and endochondral ossification, and skeletal growth. These results indicate a potential modulating role of melatonin via the MT2 receptor on abnormal osteogenic and chondrogenic differentiaation in patients with AIS.
Department of Spine Surgery, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Chong
C
Chen
Research Center of Translational Medicine, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Caixia
C
Xu
Department of Spine Surgery, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Taifeng
T
Zhou
Department of Orthopedic Surgery, Sun Yat‑sen Memorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
Bo
B
Gao
Department of Spine Surgery, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Hang
H
Zhou
Department of Zoology, School of Life Sciences, Sun Yat‑sen University, Guangzhou, Guangdong 510275, P.R. China.
Changhua
C
Chen
Department of Zoology, School of Life Sciences, Sun Yat‑sen University, Guangzhou, Guangdong 510275, P.R. China.
Changli
C
Zhang
Department of Orthopedic Surgery, Sun Yat‑sen Memorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
Dongsheng
D
Huang
Department of Spine Surgery, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Peiqiang
P
Su
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects*; D020219:Chondrogenesis / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D012600:Scoliosis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
D015415:Biomarkers; D008668:Metallothionein; D000469:Alkaline Phosphatase; D008550:Melatonin