Molecular basis of the bone disorders in patients with acromegaly are largely unknown.
Objective: To investigate gene expression profiles that regulate bone metabolism in bone tissue samples from patients with acromegaly.
Materials and Methods: Patients with clinically evident and biochemically proven active acromegaly and patients with hormonally inactive pituitary adenoma matched by age, sex and BMI were invited to participate. Bone samples were taken during transsphenoidal adenomectomy from the base of the sella-turcica, immediately placed in lysis buffer (QIAzol) and subjected to homogenization. Insulin-like growth factor 1 (IGF-1) was measured by an electrochemiluminescence assay on a Liaison. Total RNA isolation from bone tissue with on-cjlumn digestion of the genomic DNA was carried out with miRNeasy Mini Kit on the automatic station QIAcube. Reverse transcription was carried out using a High-Capacity RNA-to-cDNA Kit. Gene expression analysis was performed by Real-Time PCR on StepOnePlus instrument with Custom TaqMan Array 48 Plus plates, TaqMan Advanced miRNA Assays.
Results: We enrolled 21 subjects (12 patients with acromegaly and 9 with hormonally inactive pituitary adenomas); 13 females and 8 males, the mean age was 38 years (confident interval (CI) 95% 3343) mean BMI 28 (CI95% 2531) kg/m2. There were no significant difference within the groups. Mean IGF-1 in subjects with acromegaly 785 (CI95% 5271042) ng/ml. The expression of SOST 5,7 (CI95% 1,0110,44, P=0.022), DKK1 7,97 (CI95% 4,411,54, P<0.001), BGLAP 1,51 (CI95% 0.822,19, P<0.001) was increased in subjects with acromegaly as compared to inactive pituitary adenoma. miRNA 199a-5p 0,37 (CI95% 0.060,68, P=0.023) was suppressed.
Conclusion: In spite of increased expression of Wnt signaling antagonist, bone formation is not suppressed in subjects with acromegaly. The suppression of miRNA might explain the predominant differentiation to the cartilage tissue.
Disclosures: This study was supported by the Russian Science Foundation (grant # 15-1530032).
20 May 2017 - 23 May 2017