OBJECTIVETo determine the role of serine residues at position 63-84 of CITED1 in the nuclear translocation of CITED1 and osteoblast differentiation.

METHODSWe engineered all the 9 phosphorylated serine residues of CITED1 with a serine-to-alanine mutation at position 63-84. MC3T3E1 cells transfected with pCDNA3-CFP-CITED1 63-84 (9S>A), pCDNA3-CFP-CITED1, and vehicle plasmid were examined with confocal laser scanning microscopy before and after treatment with 100 nmol/L parathyroid hormone [PTH(1-34)] to observe the changes in the intracellular localization of CITED1. The transfected cells were induced for osteoblastic differentiation with mineralized solution in the absence or presence of 10 nmol/L PTH(1-34), and the changes in ALP activity and Ca(2+) concentration were measured; RT-PCR was used to detect the changes in ALP2, RUNX2, and OC gene expressions after the treatments.

RESULTSs PTH(1-34) promoted the nuclear translocation of CITED1 in MC3T3-E1 cells. The (63-84) 9S>A mutation of CITED1 obviously suppressed its translocation and increased ALP activity and Ca(2+) levels in the cells, which led to enhanced mineralization in the cells with also increased expressions of ALP2, RUNX2, and OC.

CONCLUSIONThe serine residues at position 63-84 of CITED1 play a vital role in the nuclear translocation of CITED1 and osteoblast differentiation.

Active Transport, Cell Nucleus ; Animals ; Cell Differentiation ; Cell Line ; Cell Nucleus ; Mice ; Mice, Inbred C57BL ; Mutation ; Nuclear Proteins ; metabolism ; Osteoblasts ; cytology ; Plasmids ; Serine ; metabolism ; Trans-Activators ; metabolism

OBJECTIVETo assess the effect of intermittent subcutaneous injections of signal-selective parathyroid hormone (PTH) peptide analog on fracture healing in orchiectomized mouse models.

METHODSThirty-six 7-week-old C57/BL male mice were orchiectomized and injected with hPTH(1-34), the signal-selective PTH peptide analog [Gly(1), Arg(19)]hPTH (1-34), or an identical volume of vehicle 1 week after induction of femoral fracture. At 14 and 28 days after the operation, the mice were sacrificed for measurement of bone mineral density (BMD) and bone mineral content (BMC) of the callus using by dual energy X-ray absorptiometry. The bone healing was evaluated by radiography, biomechanical testing, micro-computed tomography (Micro-CT) and histological examination.

RESULTSAt 14 days after the operation, BMD in PTH peptide analog group was significantly increased (P<0.05). The mouse models treated with the PTH peptide analog showed significantly lower ultimate bending force and bending rigidity than those with hPTH(1-34) treatment. X-ray and Micro-CT scanning showed that callus transformation and remodeling was better in PTH peptide analog group than in the vehicle control group but poorer than in hPTH(1-34) group.

CONCLUSIONThe signaling-selective PTH peptide analog G1, R19 (1-28) can accelerate fracture healing in orchiectomized mouse models, in which process cAMP/PKA pathway plays an important role.

Animals ; Bone Density ; Fracture Healing ; drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Orchiectomy ; Parathyroid Hormone ; analogs & derivatives ; pharmacology ; Signal Transduction

Objective:To compare the clinical outcomes between modified percutaneous kyphoplasty (PKP) and conventional PKP in the treatment of Kümmell disease.Methods:A retrospective cohort study was conducted of the 57 patients with single level kummell disease who had undergone PKP between January 2015 and December 2017 at Department of Spinal Surgery, Jiangmen Hospital Affiliated to Sun Yat-sen Uni-versity.Of them, 36 received modified PKP and 21 conventional PKP.In the modified PKP group, there were 24 males and 12 females with an age of 73.9 years±9.4 years and a course of disease of 2.2 months±1.5 months; the disease was located at a thorocic vertebra in 20 cases and at a lumbar vertebra in 16.In the conventional PKP group, there were 15 males and 6 females with an age of 72.6 years±11.9 years and a course of disease of 1.8 months±1.1 months; the disease was located at a thorocic vertebra in 10 cases and at a lumbar vertebra in 11.The 2 groups were compared in terms of operation time, bone cement volume, cement leakage, visual analogue scale (VAS), Oswestry disability index (ODI), anterior and middle heights and cobb angle of injured vertebra at postoperative 3 days, 1 and 3 months, and final follow-up.Results:There were no significant differences in the general clinical data between the 2 groups, showing compatibility between groups ( P>0.05).All the operations were accomplished uneventfully with no such serious complications as spinal cord nerve injury, wound infection, pulmonary embolism, bone cement poisoning reaction or death. There was no significant difference between the 2 groups in operation time or bone cement volume ( P>0.05).The rate of cement leakage in the modified PKP group [33.3%(9/27)] was significantly lower than that [52.4%(11/21)] in the conventional PKP group ( P<0.05).There were no significant differences be-tween the 2 groups in VAS, ODI, anterior or middle height of injured vertebra or cobb angle at postoperative 3 days or one month ( P>0.05), but the postoperative values were improved compared to the preoperative ones.At postoperative 3 months and final follow-up, the modified PKP group was significantly better in all the indexes than the conventional PKP group ( P<0.05). Conclusion:Compared with conventional PKP, the modified PKP may lead to better outcomes for Kümmell disease.