The calcium channel TRPV6 is a novel regulator of RANKL-induced osteoclastic differentiation and bone absorption activity through the IGF-PI3K-AKT pathway.

OBJECTIVES: Calcium ion signals are important for osteoclast differentiation. Transient receptor potential vanilloid 6 (TRPV6) is a regulator of bone homeostasis. However, it was unclear whether TRPV6 was involved in osteoclast formation. Therefore, the aim of this study was to evaluate the role of TPRV6 in bone metabolism and to clarify its regulatory role in osteoclasts at the cellular level. MATERIALS AND METHODS: Bone structure and histological changes in Trpv6 knockout mice were examined using micro-computed tomography and histological analyses. To investigate the effects of Trpv6 on osteoclast function, we silenced or overexpressed Trpv6 in osteoclasts via lentivirus transfection, respectively. Osteoclast differentiation and bone resorption viability were measured by tartrate-resistant acid phosphatase (TRAP) staining and pit formation assays. The expression of osteoclast marker genes, including cathepsin k, DC-STAMP, Atp6v0d2 and TRAP, was measured by qRT-PCR. Cell immunofluorescence and Western blotting were applied to explore the mechanisms by which the IGF-PI3K-AKT pathway was involved in the regulation of osteoclast formation and bone resorption by Trpv6. RESULTS: We found that knockout of Trpv6 induced osteoporosis and enhanced bone resorption in mice, but did not affect bone formation. Further studies showed that Trpv6, which was distributed on the cell membrane of osteoclasts, acted as a negative regulator for osteoclast differentiation and function. Mechanistically, Trpv6 suppressed osteoclastogenesis by decreasing the ratios of phosphoprotein/total protein in the IGF-PI3K-AKT signalling pathway. Blocking of the IGF-PI3K-AKT pathway significantly alleviated the inhibitory effect of Trpv6 on osteoclasts formation. CONCLUSIONS: Our study confirmed the important role of Trpv6 in bone metabolism and clarified its regulatory role in osteoclasts at the cellular level. Taken together, this study may inspire a new strategy for the treatment of osteoporosis.

Treatment of pelvic fractures through a less invasive ilioinguinal approach combined with a minimally invasive posterior approach.

BACKGROUND: Unstable pelvic fractures usually result from high-energy trauma. There are several treatment modalities available. The purpose of this study was to evaluate the clinical application of a new less invasive ilioinguinal approach combined with a minimally invasive posterior approach technique in patients with unstable pelvic fractures. We also address the feasibility, validity, and limitations of the technique. METHODS: Thirty-seven patients with unstable pelvic fractures were treated with our minimally invasive technique. The anterior pelvic ring fractures were treated with a less invasive ilioinguinal approach, and the sacral fractures were treated with a minimally invasive posterior approach. The clinical outcome was measured using the Majeed scoring system, and the quality of fracture reduction was evaluated. The patients were followed up for 13 to 60 months (mean, 24 months). RESULTS: Anatomical or near to anatomical reduction was achieved in 26 (70.3 %) of the anterior pelvic ring fractures and a satisfactory result was obtained in another 11(29.7 %). For the posterior sacral fractures, excellent reduction was obtained in 33 (89.2 %) of the fractures, with a residual deformity in the other 4 patients. One superficial wound infection and two deep vein thromboses occurred, all of which resolved with conservative treatment. The clinical outcome at one year was "excellent" in 29 patients and "good" in 8 patients (Majeed score). CONCLUSIONS: The satisfactory results showed that a reduction and fixation of unstable pelvic fractures is possible through a combination of a limited ilioinguinal approach and posterior pelvic ring fixation. We believe our method is a new and effective alternative in the management of pelvic fractures.

Early molecular responses of bone to estrogen deficiency induced by ovariectomy in rats.

OBJECTIVE: The study was performed to investigate bone deteriorations and the molecular responses of bone to early estrogen deficiency induced by ovariectomy (OVX) in rats. METHODS: The female rats were subjected to OVX (4 or 8 week) and sham (4 or 8 week) operation. All rats were killed 4 week or 8 week after the surgical operation. The biomarkers in serum and urine were measured. Hematoxylin & Eosin and tartate-resistant acid phosphatase staining were performed on paraffin-embedded bone sections. Expression of genes and proteins were analyzed by reverse transcription polymerase chain reaction and western blotting respectively. RESULTS: The OVX rats showed the decreased level of serum Ca and the increased level of urinary Ca excretion at 8 week post-OVX. The level of PTH and TRACP-5b increased at 4 and 8 week post-OVX. At both 4 and 8 week, FGF-23 was significantly lower in OVX rats than sham rats. The H&E staining showed remarkable bone abnormalities, including increased disconnections and separation of trabecular bone network in proximal metaphysis of tibia at OVX (4 and 8 week) group. In addition, the mRNA expression ratio of OPG/RANKL was reduced in the proximal tibia. The mRNA expression of MMP-9, CAII, EphA2 and ephrinA2, and the protein expression of EphA2 and ephrinA2 were markedly up-regulated in the proximal tibia. Moreover, the mRNA expression of TGF-ß, EphB4 and ephrinB2, and the protein expression of EphB4 and ephrinB2 were down-regulated in proximal metaphysis of tibia at OVX group. CONCLUSIONS: The endogenous estrogen deficiency was detrimental to bone, and the underlying mechanism was mediated, at least partially, through the local bone Eph/ephrin signaling pathway.

An osteotomy anterolateral approach for lateral tibial plateau fractures merged with relatively simple and intact posterolateral corner displacement.

INTRODUCTION: This study investigates the safety and efficacy of anterolateral (AL) osteotomy for the treatment of lateral tibial plateau fractures merged with relatively simple and intact posterolateral (PL) corner displacement and screens applicable patients. METHODS: Totally, 11 patients with lateral tibial plateau fractures involving the PL corner were included in this study. Of them, seven patients sustained their injuries from motor vehicle accidents (MVAs), three from sports and one from fall from height. All of them received open reduction and internal fixation through the AL approach. Operation time, incision length, range of motion (ROM), Hospital for Special Surgery (HSS) knee score, time of union and complications were retrospectively reviewed. Tibial plateau angle (TPA), lateral posterior slope angle (PSA) and articular step-off reduction after surgery were examined by a radiograph technique. RESULTS: Statistically, the means of operation time, incision length, ROM and follow-up period were 82 min, 11 cm, 97° and 27 months, respectively. Three patients had slight complications: superficial infection, hardware irritation and secondary valgus deformity, without severe neural or vascular injuries, which revealed the safety and efficacy of the PL treatment. The average HSS knee score was 91.2 (range 86-96). Reduction (mean TPA 87.2° and mean PSA 8.3°) was satisfactory in 10 patients, except for one patient with a radiographic articular step-off of 5 mm (case 10). CONCLUSIONS: The AL approach is safe and effective for lateral tibial plateau fractures involving the PL corner, especially for fractures merged with simple and intact PL corner displacement (depression and/or split).

Removal of a broken guide wire entrapped in a fractured femoral neck.

Guide wire plays an important role in the fixation of femoral neck fracture with dynamic hip screw (DHS). Breakage of a guide wire during operation is a very rare condition. We met such a dilemma in DHS fixation of a 54-year-old male patient who sustained Garden type IV fracture of the right femoral neck. The distal end of the guide wire broke and was entrapped in the fractured femoral neck. We tried to get the broken part out by a cannulated drill. Reaming was started with the cannulated drill slowly rotating around the guide K-wire until the reamer fully contained the target under fluoroscope. A bone curette was used to get the broken wire out but failed, so we had to use the cannuated drill to dredge this bone tunnel. Finally the broken wire end was taken out, mixed with blood and bone fragments. Through the existing drilling channel, DHS fixation was easily finished. The patient had an uneventful recovery without avascular necrosis of femoral head or non-union of the fracture at one year's follow-up. A few methods can be adopted to deal with the broken guide wire. The way used in our case is less invasive but technically challenging. When the guide wire is properly positioned, this method is very practical and useful.

[Diagnosis and treatment for the injury of cervical disc and longitudinal ligament].

OBJECTIVES: To study the diagnosis and treatment for the injury of cervical disc and longitudinal ligament. METHODS: From 2001 to 2005, the clinical data of sixty-three patients with cervical disc and longitudinal ligament injury were studied. Early treatment was done based on spinal cord injuries and spinal stabilities by X rays and MRI. Early operation was done in fifty-four cases and early non-operation in nine cases. RESULTS: The follow-up time was six to forty-one months in all patients. The neurological recovery was found in two of eight complete SCI post-operation, thirty-one in thirty-nine incomplete SCI. Cervical collar or plaster orthotic were used in nine cases with four to six weeks. Evidence of instability was noted in four patients, who were operated with anterior decompression fusion. Neck chronic pain was found in two patients, anterior decompression and fusion was done in one with cervical spinal cord compression. CONCLUSIONS: MRI examination is the most value measure for the diagnosis of cervical disc and longitudinal ligament injury. Early anterior decompression and fusion was an important approach for cervical disc and longitudinal ligament injury.

[Effect of high level spinal cord injury on rat heart function].

OBJECTIVE: To study the effects of high level spinal cord injury (SCI) on rat heart, and investigate the role of endothelin-1 (ET-1) in the harmful effects on heart after SCI. METHODS: Forty-eight male SD rats were randomly divided into six groups of 8 animals each: control group; 4-hour group: 4 th hour after injury to spinal cord at cervical 7 level; 12-hour group: 12 th hour after injury to 7 spinal cord at C7 level; 24-hour group with same injury; 48-hour group and 72-hour group, all with same injury. Mean arterial pressure (MAP), heart rate (HR), left ventricle systolic pressure (LVSP), and left ventricular maximum velocities of contraction (+/-dp/dt max) were recorded in each group. Lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB) and ET-1 contents in the myocardium. were also measured. Specimens of the myocardium were harvested for ultrastructure examination with transmission electron microscopy. RESULTS: Hemodynamics variables including HR, MAP, LVSP and+/-dp/dtmax were significantly decreased in all the injury groups compared with that of control group (P<0.05 or P<0.01). These variables in 12-hour group showed lowest values among all the groups (all P<0.01). But the values of cardiac enzymes were much higher in five injury groups compared with that of control group (P<0.05 or P<0.01). ET-1 contents in serum and cardiac tissue raised markedly after the injury was inflicted to the animals (P<0.05), reaching peak at 12 hours (P<0.01). Ultrastructural examination of the myocardial tissue demonstrated that there were mild dissolution of myocardial fibrils and vacuolation of mitochondria at 12 hours after injury. CONCLUSION: High level SCI could induce myocardial injuries and an excessive production of ET-1 in circulation and myocardial tissue might play a role in myocardial damage after injury of the spinal cord at a high level.