The role of miR-150 regulates bone cell differentiation and function.

BACKGROUND: mir-RNAs play a role in regulating bone homeostasis. In this study we assessed the functional role of mir-RNA 150 in bone homeostasis. We also assess the effects of miR-150 deficiency on osteoblast and osteoclast differentiation and function using in vivo and in vitro approaches. METHODS: Wild type (WT) (C57BL/6J) and miR-150 KO mice were compared for a variety of parameters. Micro-CT imaging was conducted to quantify trabecular bone mass inferior to the distal growth plate of the femur. Von Kossa staining was performed for osteoblast culture mineralization. RT-qPCR, biochemical analysis and bone histomorphometry were utilized for quantification of relevant genes and serum protein measurements. Differentiation and function of osteoblasts and osteoclasts was performed using primarily cultures and assessed the cell autonomous response of mir-RNA-150 on cell differentiation and function. RESULTS: Mir-150 exhibited expression in a variety of tissues and increases progressively with age. Through micro-CT imaging, we found that KO mice presented reduced bone mass at 4, 8, and 16 weeks of age compared to WT mice. Furthermore, histomorphometric analysis revealed increased trabecular separation, decreased bone thickness, and decreased osteoblast number in KO compared to WT mice. Mir-150 deficiency also correlated with higher bone resorption, accompanied with significant increases in CTX-1 serum levels, and a decrease in cell apoptotic rate ex vivo. Additionally, miR-150 KO mice showed increased osteoblast differentiation and decreased osteoclastogenesis ex vivo. Luciferase assay showed increased Osteoactivin/GPNMB expression in miR-150 KO osteoblasts compared to WT cells. CONCLUSION: Our data suggests that miR-150 influences osteoblast and osteoclast functionality and differentiation; specifically, miR-150 serves as a negative regulator for osteoblasts and a positive regulator for osteoclasts by regulating, at least in part, Osteoactivin/GPNMB expression.

Arthroscopic validation of the clinical exam for the detection of the symptomatic synovial-plical complex by relief from surgical excision.

PURPOSE: The goal is to introduce a reproducible exam technique that allows clinical diagnosis of symptomatic plical bands and associated synovium about the knee. We then aimed to assess the accuracy of the exam technique through arthroscopic confirmation of these tissues. Lastly, we hope to determine whether arthroscopic plicectomy and partial synovectomy is an effective treatment for alleviating the pain associated with symptomatic plica. METHODS: This retrospective study evaluated 80 consecutive symptomatic knees under the care of a single physician diagnosed with symptomatic plica and associated painful synovium from 2001-2011. These patients underwent diagnostic and therapeutic arthroscopy to verify the presence of a plica and painful synovium with plicectomy and partial synovectomy if necessary. Statistical analysis was performed to determine the sensitivity and positive predictive value of the exam. RESULTS: The medial parapatellar region was the most common location for symptomatic plica and associated synovial tissue. The exam technique described in this study had a sensitivity of 83.8% with a positive predictive value of 98.6% in the specific patient population described. CONCLUSIONS: This study suggests that while the medial plical band is the most common, there is frequently sensitive synovial tissue found in multiple locations about the knee. This study also suggests that a thorough exam technique can accurately diagnose both the plical bands as well as the sensitive synovial tissue. LEVEL OF EVIDENCE: Level II, Diagnostic Study. See the Guidelines for Authors for a complete description of levels of evidence.

A clinical and radiographic approach for establishing proper tibial tubercle transfer when using quad active femoral nerve stimulation.

BACKGROUND: The tibial tubercle-trochlear groove measurement (TT-TG), which measures the lateral offset of the tibial tubercle relative to the trochlear groove of the femur, has been utilized as an intraoperative tool to help establish maximum patellofemoral congruency in patients who suffer from patellar instability. We have previously published our approach of establishing how far to transfer the tibial tubercle using intraoperative femoral nerve stimulation in order to achieve congruency from 0-30° of flexion. The technique and clinical outcomes have previously been published in this journal and elsewhere. Here we describe the use of the TT-TG distance to determine how far to transfer the tibial tubercle to achieve our goals and have found that it varies according to the clinical exam features. PURPOSE: We intended to determine the effectiveness of using the preoperatively established TT-TG to predict the degree of intraoperative me- dialization of the tibial tubercle to achieve our goal of establishing dynamic congruency of the patella in the trochlear groove when using the previously described femoral nerve stimulation method of estimating dynamic tracking of the patella. METHODS: From the study group of patients used in other publications, we examined 20 knees in 18 patients who had a history of recurrent lateral dislocations and underwent a Fulkerson tibial tubercle transfer. Each knee was dynamically assessed preoperatively by obtaining an MRI at 30° of flexion and complete hyperextension while voluntarily contracting their quadriceps. These were then compared to the intraoperative transfer of the tibial tubercle required to achieve maximum congruency when the femoral nerve was stimulated. We then looked at the preoperative TT-TG measurement to determine its role in predicting what was required at achieving congruency in the context of the quad active MRI findings. RESULTS: Thirteen knees preoperatively demonstrated a positive J-sign defined as the patella subluxated greater than or equal to 5 mm lateral in full extension compared to 30° of flexion. In these patients, the TT-TG was accurate if the distance medialized was 1:1 with the measured TT-TG. In 7 out of the 20 knees, the patella demonstrated a false negative J-sign where the patella was radio- graphically subluxated at 30° of flexion as well as at hyperextension. In this group, the TT-TG underestimated the transfer required for congruency on average 5mm even when using the 1:1 ratio. CONCLUSIONS: The preoperative use of the J-sign is of value when determining the role of the TT-TG measurement and estimating the distance required to intraoperatively achieve congruency when using the femoral nerve stimulation technique. Those that demonstrated a positive J-sign of 5mm or greater, a 1:1 ratio of TT-TG to medialization is most reliable at establishing congruency of the patellofemoral joint. Whereas, those that demonstrated a false negative J-sign even the 1:1 ratio remains inadequate at producing congruency and more medialization is required. LEVEL OF EVIDENCE: Level III, Retrospective Observational/Comparative Study.