Abstract | STUDY DESIGN: In vitro assays were performed with bone-forming cells isolated from 41 patients with adolescent idiopathic scoliosis and 17 control patients exhibiting another type of scoliosis or none. OBJECTIVE: To determine whether a dysfunction of the melatonin-signaling pathway in tissues targeted by this hormone is involved in adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA:
Pinealectomy in chicken has led to the formation of a scoliotic deformity, thereby suggesting that a melatonin deficiency may be at the source of adolescent idiopathic scoliosis. However, the relevance of melatonin in the etiopathogenesis of that condition is controversial because most studies have reported no significant change in circulating levels of melatonin in patients with adolescent idiopathic scoliosis. METHODS: Primary osteoblast cultures prepared from bone specimens obtained intraoperatively during spine surgeries were used to test the ability of melatonin and Gpp(NH)p, a GTP analogue, to block cAMP accumulation induced by forskolin. In parallel, melatonin receptor and Gi protein functions were evaluated by immunohistochemistry and by coimmunoprecipitation experiments. RESULTS: The cAMP assays demonstrated that melatonin signaling was impaired in osteoblasts isolated from adolescent idiopathic scoliosis patients to different degrees allowing their classification in 3 distinct groups based on their responsiveness to melatonin or Gpp(NH)p. CONCLUSION:
Melatonin signaling is clearly impaired in osteoblasts of all patients with adolescent idiopathic scoliosis tested. Classification of patients with adolescent idiopathic scoliosis in 3 groups based on functional in vitro assays suggests the presence of distinct mutations interfering with the melatonin signal transduction. Posttranslational modifications affecting Gi protein function, such as serine residues phosphorylation, should be considered as one possible mechanism in the etiopathogenesis of AIS.
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Authors | Alain Moreau, Da Shen Wang, Steve Forget, Bouziane Azeddine, Debora Angeloni, Franco Fraschini, Hubert Labelle, Benoît Poitras, Charles-Hilaire Rivard, Guy Grimard |
Journal | Spine
(Spine (Phila Pa 1976))
Vol. 29
Issue 16
Pg. 1772-81
(Aug 15 2004)
ISSN: 1528-1159 [Electronic] United States |
PMID | 15303021
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptor, Melatonin, MT1
- Receptor, Melatonin, MT2
- Colforsin
- Guanylyl Imidodiphosphate
- Cyclic AMP
- Adenylyl Cyclases
- Melatonin
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Topics |
- Adenylyl Cyclases
(metabolism)
- Adolescent
- Cells, Cultured
- Colforsin
- Cyclic AMP
(metabolism)
- Female
- Guanylyl Imidodiphosphate
- Humans
- Immunoenzyme Techniques
- Male
- Melatonin
(physiology)
- Osteoblasts
(metabolism)
- Receptor, Melatonin, MT1
(metabolism)
- Receptor, Melatonin, MT2
(metabolism)
- Scoliosis
(etiology, metabolism, pathology)
- Signal Transduction
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