Loss of Sirtuin 6 in osteoblast lineage cells activates osteoclasts, resulting in osteopenia.

Adult bone homeostasis requires a fine-tuned balance between the activity of osteoblasts and osteoclasts. This osteoblast-osteoclast coupling is therapeutically important because it limits the efficacy of most anabolic or anti-resorptive treatments for osteoporosis. Sirtuin6 (SIRT6), a histone deacetylase, was implicated recently as an important regulator in bone homeostasis, but its in vivo function in osteoblast lineage cells remains unclear, mainly due to a lack of in vivo experiments with osteoblast lineage-specific Sirt6 knockout mice. Here, we show that Sirt6 in mature osteoblasts and/or osteocytes inhibits osteoclastogenesis via a paracrine mechanism. We found that osteoblast/osteocyte-specific Sirt6 knockout mice show reduced bone mass due to increased osteoclast formation. Mechanistically, we attribute this increased osteoclastogenesis to decreased osteoprotegerin expression in Sirt6-null osteoblasts and osteocytes. This loss of Sirt6 in osteoblasts and osteocytes does not, however, alter bone formation parameters in vivo. It does accelerate osteogenic differentiation in ex vivo culture, indicating that the osteoblast/osteocyte-autonomous functions of SIRT6 have minor effects on the osteopenic phenotype. These results establish a critical role for SIRT6 in mature osteoblasts and osteocytes in adult bone homeostasis as a negative paracrine regulator of osteoclastogenesis.

Five-year investigation of a large orthodontic patient population at a dental hospital in South Korea.

OBJECTIVE: The purpose of this study was to investigate the characteristics of orthodontic patients at Yonsei Dental Hospital from 2008 to 2012. METHODS: We evaluated Angle's classification from molar relationships, classification of skeletal malocclusion from the A point-nasion-B point angle, facial asymmetry, and temporomandibular joint disorders (TMDs) from the records of 7,476 patients who received an orthodontic diagnosis. The orthognathic surgery rate, extraction rate, and extraction sites were determined from the records of 4,861 treated patients. RESULTS: The patient number increased until 2010 and gradually decreased thereafter. Most patients were aged 19-39 years, with a gradual increase in patients aged ≥ 40 years. Angle's Class I, Class II divisions 1 and 2, and Class III malocclusions were observed in 27.7%, 25.6%, 10.6%, and 36.1% patients, respectively, with a gradual decrease in the frequency of Class I malocclusion. The proportion of patients with skeletal Class I, Class II, and Class III malocclusions was 34.3%, 34.3%, and 31.4%, respectively, while the prevalence of facial asymmetry and TMDs was 11.0% and 24.9%, respectively. The orthognathic surgery rate was 18.5%, with 70% surgical patients exhibiting skeletal Class III malocclusion. The overall extraction rate among nonsurgical patients was 35.4%, and the maxillary and mandibular first premolars were the most commonly extracted teeth. CONCLUSIONS: The most noticeable changes over time included a decrease in the patient number after 2010, an increase in the average patient age, and a decrease in the frequency of Angle's Class I malocclusion. Our results suggest that periodic characterization is necessary to meet the changing demands of orthodontic patients.

pSVPoMcat modifying Schwann cell to protect injured spinal neurons in rats.

OBJECTIVE: To investigate the protective effect of pSVPoMcat (myelin basic protein microgene) modifying Schwann cell on injured spinal neurons. METHODS: A model of rat spinal cord injured by hemisection was used. One hundred and twenty healthy SD rats of both sexes weighing 250-300 g were divided into three groups: Group A (n=40, treated with implantation of pSVPoMcat modifying Schwann cell), Group B (n= 40, treated with implantation of Schwann cell only) and Group C (n=400, treated with sham operation as the control). One week after operation the rat functional recovery was observed dynamically by using combined behavioral score (CBS) and cortical somatasensory evoked potentials, the spinal cord sections were stained by Nissl, acid phosphatase enzyme histochemistry and cell apoptosis was examined by methye green, terminal deoxynucleotidyl and the dUTP Nick end labeling technique. Quantitative analysis was done by computer image analysis system. RESULTS: In Group A the injured neurons recovered well morphologically. The imaging analysis showed a result of Group A

Repair effect of Schwann cells modified by microgene pSVPoMcat on injured spinal cord in rats.

OBJECTIVE: To observe the repair effect of Schwann cells (SCs) modified by microgene pSVPoMcat on injured spinal cord in rats. METHODS: Semi-transection injury at the level of T(8) of spinal cord was made with cutting method on 120 Sprague Dawley (SD) rats. Then 40 rats implanted with SCs modified by microgene pSVPoMcat were taken as Group A, 40 rats implanted with simple SCs as Group B and the other 40 rats were taken as the control group (Group C). The functional recovery of the rats was observed through combined behavioral score (CBS) and cortical somatosensory evoked potential (CSEP), and the expression of the glial fibrillary acidic protein (GFAP) was measured with in situ hybridization and immunocytochemistry. At 3 months after operation, the rats were examined with magnetic resonance image (MRI), and the neurofilaments (NF) of the axons were stained with immunohistochemical method. RESULTS: GFAP expression in Group A was significantly lower than that of the other 2 groups. MRI showed that the spinal signals in the injured area recovered fundamentally in Group A, didn't recover in Group B and malacia focus was found in Group C, which was same as the results of NF staining. Wave amplitudes in incubation periods in Group A and Group B tended to recover. It recovered to the normal level in Group A, which was similar to the results of CBS. CONCLUSIONS: SCs modified by microgene pSVPoMcat can inhibit GFAP expression, improve the growth of the axons and the functional recovery of neurons after spinal cord injury.