Premium
Expression of the melatonin receptor (MT) 1 in benign and malignant human bone tumors
Author(s) -
Toma Cyril D.,
Svoboda Martin,
Arrich Ferdi,
Ekmekcioglu Cem,
Assadian Ojan,
Thalhammer Theresia
Publication year - 2007
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2007.00464.x
Subject(s) - rankl , osteoprotegerin , osteoclast , osteosarcoma , stromal cell , endocrinology , melatonin , medicine , osteoblast , receptor , bone marrow , biology , messenger rna , activator (genetics) , chemistry , cancer research , biochemistry , gene , in vitro
The beneficial effects of melatonin on bone homeostasis have been shown in various diseases. As this indoleamine causes dose‐dependent modulation of bone‐forming osteoblast and bone‐resorbing osteoclast activities by receptor‐independent and ‐dependent pathways, we investigated the expression of G‐protein‐coupled melatonin receptors (MTs) in malignant and non‐malignant human bone lesions. By TaqMan polymerase chain reaction (PCR), we analyzed 30 specimens from osteosarcoma and 11 from benign bone tumors for MT1‐mRNA expression. Furthermore, we determined mRNA expression levels of the osteoclast activity‐stimulating receptor activator of nuclear factor‐ κ B ligand (RANKL) and its counterpart osteoprotegerin (OPG). Although mean MT1‐mRNA levels were similar ( P = 0.596) in malignant (4.39 ± 4.98‐fold) and benign samples (4.64 ± 6.81‐fold), the highest MT1‐mRNA levels (up to 27‐fold) were observed in individual osteosarcomas, particularly, in two specimens of patients with local recurrence of the tumor. Moreover, mean RANKL‐ and OPG‐mRNA levels were similar in malignant and benign specimens (RANKL: 7.38 ± 9.61‐fold versus 3.57 ± 3.11‐fold, P = 0.207; OPG: 23.45 ± 32.76 versus 8.07 ± 7.23‐fold, P = 0.133). Again, highest RANKL‐ and OPG‐mRNA levels (up to 41‐ and 160‐fold, respectively) were observed in individual osteosarcomas. Expression of MT1‐mRNA was confirmed in two human osteosarcoma cell lines (HOS, MG63). High expression levels of MT1‐mRNA together with low OPG‐mRNA were found in both osteosarcoma cell lines, while in normal human osteoblasts and bone marrow stromal cells, high OPG‐mRNA levels were associated with low MT1‐mRNA levels. These data on the abundant expression of MT1‐mRNA in human bone tumors and osteosarcoma cells lines suggest an important role for MT1 in bone pathology.