The molecular mechanisms that regulate hADSC differentiation toward osteogenic precursors and subsequent bone-forming osteoblasts is unknown. Using osteoblast precursors obtained from subcutaneous human adipose tissue, we observed that microRNA-26a modulated late osteoblasts differentiation by targeting the SMAD1 transcription factor. Introduction: Elucidation of the molecular mechanisms guiding human adipose tissue-derived stem cells (hADSCs) differentiation is of extreme importance for improving the treatment of bone-related diseases such as osteoporosis. The aim of this study was to identify microRNA as a regulator of the osteogenic differentiation of hADSCs. Materials and Methods: Osteoblast differentiation of hADSCs was induced by treatment with dexamethasone, ascorbic acid, and ␤-glycerol phosphate. The expression of osteoblastic phenotype was evaluated after the induction by simultaneous monitoring of alkaline phosphatase activity, the expression of genes involved in osteoblastic differentiation by real-time RT-PCR, and mineralization at the same time. MicroRNA expression was determined by Northern blot, and transfection of both antisense miR-RNA and sensor plasmids was done to validate the inhibitory role of microRNA during hADSC osteogenesis. Western blot was used to determine the expression levels of the SMAD1 protein. qRT-PCR analysis was used to compare the expression patterns of osteoblastic markers in transfected cells. Results and Conclusions:We analyzed the role of microRNA 26a (miR-26a) during differentiation of hADSCs. Northern blot analysis of miR-26a during hADSC differentiation showed increased expression, whereas expression of the SMAD1 protein was complementary to that of miR-26a. Because the highest expression of miR-26a and the lowest expression of SMAD1 protein were reached at hADSC terminal differentiation, we carried out our study during the late stages of hADSC differentiation. The inhibition of miR-26a, by 2Ј-O-methyl-antisense RNA, increased protein levels of its predicted target, SMAD1 transcription factor, in treated osteoblasts, upregulating bone marker genes and thus enhancing osteoblast differentiation. Our data suggest a role for miR-26a in the differentiation induced by treatment with dexamethasone, ascorbic acid, and ␤-glycerol phosphate of hADSCs toward the osteogenic lineage by targeting its predicted target, the SMAD1 protein. This study contributes to a better knowledge of molecular mechanisms governing hADSC differentiation by proposing a microRNA-based control of late differentiation.

Background The Italian Society for Orthopaedics and Traumatology conceived this guidance—which is primarily addressed to Italian orthopedic surgeons, but should also prove useful to other bone specialists and to general practitioners—in order to improve the diagnosis, prevention, and treatment of osteoporosis and its consequences.Materials and methodsLiterature reviews by a multidisciplinary team.ResultsThe following topics are covered: the role of instrumental, metabolic, and genetic evaluations in the diagnosis of osteoporosis; appraisal of the risk of fracture and thresholds for intervention; general strategies for the prevention and treatment of osteoporosis (primary and secondary prevention); the pharmacologic treatment of osteoporosis; the setting and implementation of fracture liaison services for tertiary prevention. Grade A, B, and C recommendations are provided based on the main levels of evidence (1–3). Toolboxes for everyday clinical practice are provided.ConclusionsThe first up-to-date Italian guidelines for the primary, secondary, and tertiary prevention of osteoporosis and osteoporotic fractures are presented.

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended. Definition Multiple Endocrine Neoplasia Type 1 (MEN1, OMIM 131100) is a rare inherited autosomal dominant cancer syndrome with a very high penetrance and an equal sex distribution that is characterised by the presence of hyper-plasia and neoplasia in at least two different endocrine tissues (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient. Two differ

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MicroRNAs (miRNAs) are endogenous noncoding RNAs that negatively regulate gene expression by binding the 3′ noncoding region of the messenger RNA targets inducing their cleavage or blocking the protein translation. They play important roles in multiple biological and metabolic processes, including developmental timing, signal transduction, and cell maintenance and differentiation. Their deregulation can predispose to diseases and cancer. miRNA expression has been demonstrated to be deregulated in many types of human tumors, including thyroid cancers, and could be responsible for tumor initiation and progression. In this paper we reviewed the available data on miRNA deregulation in different thyroid tumors and describe the putative role of miRNA in thyroid cancer development.