Strain-induced mechanotransduction through primary cilia, extracellular ATP, purinergic calcium signaling, and ERK1/2 transactivates CITED2 and downregulates MMP-1 and MMP-13 gene expression in chondrocytes.

OBJECTIVE: To determine the strain-induced signaling pathways involved in regulating the transactivation of the transcription regulator Cbp/p300 Interacting Transactivator with ED-rich tail 2 (CITED2) and downstream targets in chondrocytes. METHODS: Primary human chondrocytes or C28/I2 chondrocytic cells were subjected to various strain regimes. C57BL/6 mice were subjected to treadmill running. Loss-of-function was carried out using siRNA or inhibitors specific for targeted molecules. mRNA levels were assayed by RT-qPCR, and proteins by western blotting, immunofluorescence, and/or immunohistochemical staining. CITED2 promoter activity was assayed in chondrocytes using wild-type or mutant constructs. RESULTS: Cyclic strain at 5%, 1 Hz induced CITED2 expression and suppressed expression of matrix metalloproteinase (MMP)-1 and -13 at the messenger RNA (mRNA) and protein levels in human chondrocytes. Abolishing primary cilia through knockdown of intraflagellar transport protein (IFT88) attenuated CITED2 gene expression and decreased protein levels. Similar effects were observed with inhibitors of extracellular adenosine triphosphate (ATP) or P2 purinergic receptors, or antagonists of Ca(2+) signaling. Knockdown of IFT88 in articular chondrocytes in vivo diminished treadmill induced-CITED2 expression and upregulated MMPs. Knockdown of hypoxia-inducible factor (HIF)1α, specificity protein 1 (Sp1), or deletion of the shear stress response element (SSRE) in the CITED2 promoter limited cyclic strain-induced transactivation of CITED2. However, the strain induced-transactivation of CITED2 was abolished only on knockdown of HIF1α, Sp1, and SSRE or by loss-of-function of IFT88 or extracellular-signal-regulated kinases (ERK)1/2. CONCLUSIONS: CITED2 transactivation is a critical event in signaling generated by strain and transduced by primary cilia, extracellular ATP, P2 purinergic receptors, and Ca(2+) signaling. Strain-induced CITED2 transactivation requires HIF1α, Sp1, and an intact SSRE and leads to the downregulation of MMPs such as MMP-1 and MMP-13.

Cemented internal fixation for supracondylar femur fractures in osteoporotic patients.

Seventeen, supracondylar femur fractures in 15 severely osteoporotic patients (average age, 81.9 years) were treated with a 95 degree supracondylar plate and dynamic compression screw supplemented with intramedullary methyl methacrylate and massive cancellous bone graft harvested from the distal femoral metaphysis. Interfragmentary compression and rigid fracture fixation was obtained in all cases with the use of the A-O compression device. Patients were allowed early protected weight bearing without external immobilization. At follow-up observation (average, 2.1 years), bony union was noted in all cases, and knee flexion averaged 100.4 degrees. There were no malunions or cases of implant failure. Complications included two early postoperative deaths and three femur fractures above the plate. This technique was effective in rapidly restoring patient mobility while avoiding the complications of implant failure.

Clostridium perfringens and Staphylococcus epidermidis polymicrobial septic arthritis. A case report.

Septic arthritis caused by Clostridium perfringens is extremely rare. Previously there has been only one report of Clostridium perfringens in combination with an aerobe causing septic arthritis. This report presents a 23-year-old man with a mixed aerobic/anaerobic septic arthritis treated with intravenous antibiotics and repeated surgical drainage. It is the only report to date of a polymicrobial septic arthritis involving both Staphylococcus epidermidis and Clostridium perfringens. This report and a review of the literature demonstrate the existence of polymicrobial septic arthritis and illustrate its fulminant nature.

Open tibial fractures treated by anterior half-pin frame fixation.

Forty-two open tibial fractures were treated with anterior half-pin frame fixation, weight bearing as tolerated, and early reconstruction of the soft tissue envelope. Thirty fractures were followed to completion of therapy. The infection rate was 7.1%, nonunion rate, 3.0%, and pin tract infection rate, 0.5%. Problems of malunion (23.3%) and of secondary fractures around lag screws (17.6%) may be reduced by early cancellous bone grafting and limited use of minimal internal fixation.

Ender rod versus compression screw fixation of hip fractures.

Eighty-seven matched pairs of patients with extracapsular hip fractures were treated with either Ender rod or compression screw and plate fixation. The data obtained both perioperatively and from one to 39 months postoperatively showed no significant differences with respect to infection rate, mortality, length of stay, or ultimate functional status. In the Ender rod group, 66.7% of the patients experienced technical problems, compared with 10.3% of patients in the compression screw group. The Ender technique offered few practical advantages and an unacceptably high level of problems, even when patients with only stable fractures were considered.