Qiang Jie

GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic differentiation of BMMSCs

Free fatty acids display diverse effects as signalling molecules through GPCRs in addition to their involvement in cellular metabolism. GPR120, a G protein-coupled receptor for long-chain unsaturated fatty acids, has been reported to mediate adipogenesis in lipid metabolism. However, whether GPR120 also mediates osteogenesis and regulates BMMSCs remain unclear. In this study, we showed that GPR120 targeted the bi-potential differentiation of BMMSCs in a ligand dose-dependent manner. High concentrations of TUG-891 (a highly selective agonist of GPR120) promoted osteogenesis via the Ras-ERK1/2 cascade, while low concentrations elevated P38 and increased adipogenesis. The fine molecular regulation of GPR120 was implemented by up-regulating different integrin subunits (α1, α2 and β1; α5 and β3). The administration of high doses of TUG-891 rescued oestrogen-deficient bone loss in vivo, further supporting an essential role of GPR120 in bone metabolism. Our findings, for the first time, showed that GPR120-mediated cellular signalling determines the bi-potential differentiation of BMMSCs in a dose-dependent manner. Additionally, the induction of different integrin subunits was involved in the cytoplasmic regulation of a seesaw-like balance between ERK and p38 phosphorylation. These findings provide new hope for developing novel remedies to treat osteoporosis by adjusting the GPR120-mediated differentiation balance of BMMSCs.

Biomechanical evaluation of the expansive cannulated screw for fixation of femoral neck fractures

BACKGROUND Femoral neck fracture is one of the common clinical traumas, especially amongst elder patients. This study aims to test, compare and evaluate the bone-screw interface strengths, the fatigue strengths, and the stabilities of our newly designed expansive cannulated screw (ECS) and the common cannulated compression screw (CCS) in the fixation of femoral neck fracture, which is a summary of recent research. METHODS Twenty-four pairs (48) of fresh femur specimens were randomly divided into four groups with six pairs (12) in each. To simulate one-legged standing, the maximum compressive strength and the single-screw axial pull-out force were compared between the fixed femoral necks treated with two ECSs and two CCSs, two ECSs and three CCSs or three ECSs and three CCSs, respectively. The screws were also subjected to 1,000,000 cycles of a loaded fatigue test and the results were recorded. FINDINGS When the same number of screws was used, the ECS showed significantly greater maximum compressive strength than the CCS (P<0.05), but no significant difference in fixation effectiveness was detected between the two ECSs and the three CCSs groups. The maximum axial pull-out strength of the ECS was also significantly greater that of the CCS (P<0.01); however, there was no sign of fatigue in both the ECS and CCS after 1,000,000 cycles of loaded fatigue test. INTERPRETATION The ECS shows better fixation performance than the currently and commonly used CCS; under certain circumstances, fixation with two ECSs can achieve the same effect as that with traditional three CCSs.

Disturbed MEK/ERK signaling increases osteoclast activity via the Hedgehog-Gli pathway in postmenopausal osteoporosis.

Postmenopausal osteoporosis is a worldwide health problem and is characterized by increased and activated osteoclasts. However, the mechanism by which osteoclasts are dysregulated in postmenopausal osteoporosis is not fully understood. In this study, we found that the Hedgehog-Gli pathway was upregulated in postmenopausal osteoporotic osteoclasts and that 17β-estradiol both inhibited osteoclastogenesis and induced osteoclast apoptosis by downregulating Hedgehog-Gli signaling. Furthermore, we demonstrated that the Hedgehog-Gli pathway was negatively regulated by MEK/ERK signaling and that this effect was Sonic Hedgehog (SHH)-dependent and was partially blocked by an anti-SHH antibody. Moreover, we found that the stimulatory effect of Hedgehog signaling on osteoclastogenesis and the inhibitory effect on osteoclast apoptosis were dependent on the Gli family of transcription factors. The pathways and molecules that contribute to the regulation of osteoclastogenesis and apoptosis represent potential new strategies for designing molecular drugs for the treatment of postmenopausal osteoporosis.

Surgical Treatment of Dystrophic Spinal Curves Caused by Neurofibromatosis Type 1: A Retrospective Study of 26 Patients.

AbstractDystrophic scoliosis in neurofibromatosis type 1 (NF-1) is difficult to treat. The purpose of this study was to review the clinical and radiological outcome of surgical treatment of dystrophic spinal curves in NF-1, for analyzing its efficacy, safety, and possible complications.This retrospective study consisted of 26 NF-1 patients with spinal deformities treated between 2003 and 2012 in our department. Preoperative X-ray, 3D-CT, and MRI were performed to evaluate the deformities of dystrophic scoliosis accurately. All patients were treated with posterior instrumented fusion alone using screws and hooks. According to the anatomical development situation of each patients pedicles and the transverse processes, we chose different fixations and different fixed segments. The clinical and radiological outcomes of surgical correction were evaluated postoperatively.The average preoperative kyphosis was 43° (range 15–86°). The postoperative kyphosis had an average of 20° (range 10–39°) yielding 53% correction. At final follow-up, there was an average of 4.6% correction loss. The preoperative scoliosis Cobb angle had an average of 47° (range 35–96°). The postoperative scoliosis Cobb angle had an average of 21° (range 10–37°) yielding 55% correction. At final follow-up, there was an average of 6.6% correction loss. The apical vertebral body rotation was corrected by an average of 48%. At final follow-up, the score of the SRS-30 questionnaire ranged from 97 to 135 with an average of 109.In conclusion, the deformities of dystrophic scoliosis can be accurately determine through preoperative radiolographic evaluation, which plays an important role in guiding the correction of scoliosis program development. The results of this study demonstrate that satisfactory therapeutic effects can be achieved in the dystrophic scoliosis patients by preoperative meticulous surgical plans, intraoperative careful manipulation, and hybrid instrumentation.

Surgical results of developmental dysplasia of the hip in older children based on using three-dimensional computed tomography.

BACKGROUND The surgical management of developmental dysplasia of the hip (DDH) in older children has been the subject of controversy. The purpose of this study was to evaluate the outcome in patients with neglected DDH who underwent individual procedures based on using three-dimensional computed tomography. METHODS Forty-seven patients (59 hips) were treated using Pemberton osteotomy or Dega plus Pemberton osteotomy. Subtrochanteric transverse femoral shortening and derotation osteotomy were performed for all patients. The average age at the time of surgery was 10.5 y for group 1 (bilateral dislocation, 24 hips) and 11.2 y for group 2 (unilateral dislocation, 35 hips). Mean follow-up was 5.3 y for group 1 and 5.8 y for group 2. RESULTS At the end of follow-up, 13 hips (54.2%) were rated excellent, eight hips (33.3%) were good, and three hips (12.5%) were fair in group 1. In group 2, 20 hips (57.1%) were rated excellent, 10 hips (28.6%) were good, and five hips (14.3%) were fair. There were five patients who had a limb length discrepancy of approximately 1.5 cm in group 2. Six hips in group 1 and seven hips in group 2 had osteonecrosis of varying severity. CONCLUSIONS We believe that preoperation three-dimensional computed tomography evaluation, personalized operation plans, and experience with the surgical procedure are the main reasons for the satisfactory therapeutic effects achieved in this study in older children with DDH.

Prevention of growth arrest by fibrin interposition into physeal injury.

This study investigated the repair effects of fat and fibrin graft interposition through a proximal tibia transphyseal injury model and assessed the effectiveness of treatment to physeal injury with the fibrin. In this study, a unilateral growth plate injury was created in the right proximal tibia of 28 rats without any graft interposition; all left tibias were left untouched. In the other group of 28 rats, a bilateral physeal injury was made with the left tibia filled with autogenously adipose tissue and the right tibia filled with fibrin. To compare the malformed extents induced by different interventions, the length and the metaphyseal–diaphyseal angle of the tibia of three injured groups were examined. Further studies on bone density analysis and histological change were used to compare the bony bridge formation under different interventions. Results showed that the deformity angle and medial length of the tibia were significantly different between the grafted groups and nongrafted group at 4, 16, and 24 weeks postoperative (P<0.01). Results also showed no significant difference between fibrin-graft and fat-graft groups (P>0.05). Furthermore, the bone mineralization density of bony bridge induced by injury was significantly different between the grafted group and nongrafted group at 4, 16, and 24 weeks postoperative (P<0.01). Histological findings showed that bony repair after physeal injury was inhibited by both fibrin and fat interventions. We concluded that fibrin could be a substitute of adipose tissue in preventing the deformities induced by epiphyseal injury. Similar to autogenous fat, fibrin was found to alleviate limb shortness and prevent angular malformation by forming a scar instead of a bony bridge. The use of fibrin can help us to develop effective and compound intervention grafts to prevent skeletal deformity and regenerate normal cartilage tissue in the future.

Screening and validation of serum protein biomarkers for early postmenopausal osteoporosis diagnosis

Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro‑computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array‑based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases‑1 and monocyte chemotactic protein‑1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic.