Cory Edgar

BMP treatment of C3H10T1/2 mesenchymal stem cells induces both chondrogenesis and osteogenesis

The molecular mechanisms by which bone morphogenetic proteins (BMPs) promote skeletal cell differentiation were investigated in the murine mesenchymal stem cell line C3H10T1/2. Both BMP‐7 and BMP‐2 induced C3H10T1/2 cells to undergo a sequential pattern of chondrogenic followed by osteogenic differentiation that was dependent on both the concentration and the continuous presence of BMP in the growth media. Differentiation was determined by the expression of chondrogenesis and osteogenesis associated matrix genes. Subsequent experiments using BMP‐7 demonstrated that withdrawal of BMP from the growth media led to a complete loss of skeletal cell differentiation accompanied by adipogenic differentiation of these cells. Continuous treatment with BMP‐7 increased the expression of Sox9, Msx 2, and c‐fos during the periods of chondrogenic differentiation after which point their expression decreased. In contrast, Dlx 5 expression was induced by BMP‐7 treatment and remained elevated throughout the time‐course of skeletal cell differentiation. Runx2/Cbfa1 was not detected by ribonuclease protection assay (RPA) and did not appear to be induced by BMP‐7. The sequential nature of differentiation of chondrocytic and osteoblastic cells and the necessity for continuous BMP treatment to maintain skeletal cell differentiation suggests that the maintenance of selective differentiation of the two skeletal cell lineages might be dependent on BMP‐7‐regulated expression of other morphogenetic factors. An examination of the expression of Wnt, transforming growth factor‐β (TGF‐β), and the hedgehog family of morphogens showed that Wnt 5b, Wnt 11, BMP‐4, growth and differentiation factor‐1 (GDF‐1), Sonic hedgehog (Shh), and Indian hedgehog (Ihh) were endogenously expressed by C3H10T1/2 cells. Wnt 11, BMP‐4, and GDF‐1 expression were inhibited by BMP‐7 treatment in a dose‐dependent manner while Wnt 5b and Shh were selectively induced by BMP‐7 during the period of chondrogenic differentiation. Ihh expression also showed induction by BMP‐7 treatment, however, the period of maximal expression was during the later time‐points, corresponding to osteogenic differentiation. An interesting phenomenon was that BMP‐7 activity could be further enhanced twofold by growing the cells in a more nutrient‐rich media. In summary, the murine mesenchymal stem cell line C3H10T1/2 was induced to follow an endochondral sequence of chondrogenic and osteogenic differentiation dependent on both dose and continual presence of BMP‐7 and enhanced by a nutrient‐rich media. Our preliminary results suggest that the induction of osteogenesis is dependent on the secondary regulation of factors that control osteogenesis through an autocrine mechanism.

Current Concepts in the Treatment of Acromioclavicular Joint Dislocations

PURPOSE To conduct a systematic review of the literature in relation to 3 considerations in determining treatment options for patients with acromioclavicular (AC) joint dislocations: (1) operative versus nonoperative management, (2) early versus delayed surgical intervention, and (3) anatomic versus nonanatomic techniques. METHODS The PubMed database was searched in October 2011 using the single term acromioclavicular and the following search limits: any date, humans, English, and all adult (19+). Studies were included if they compared operative with nonoperative treatment, early with delayed surgical intervention, or anatomic with nonanatomic surgical techniques. Exclusion criteria consisted of the following: Level V evidence, laboratory studies, radiographic studies, biomechanical studies, fractures or revisions, meta-analyses, and studies reporting preliminary results. RESULTS This query resulted in 821 citations. Of these, 617 were excluded based on the title of the study. The abstracts and articles were reviewed, which resulted in the final group of 20 studies that consisted of 14 comparing operative with nonoperative treatment, 4 comparing early with delayed surgical intervention, and 2 comparing anatomic with nonanatomic surgical techniques. The lack of higher level evidence prompted review of previously excluded studies in an effort to explore patterns of publication related to operative treatment of the AC joint. This review identified 120 studies describing 162 techniques for operative reconstruction of the AC joint. CONCLUSIONS There is a lack of evidence to support treatment options for patients with AC joint dislocations. Although there is a general consensus for nonoperative treatment of Rockwood type I and II lesions, initial nonsurgical treatment of type III lesions, and operative intervention for Rockwood type IV to VI lesions, further research is needed to determine if differences exist regarding early versus delayed surgical intervention and anatomic versus nonanatomic surgical techniques in the treatment of patients with AC joint dislocations. LEVEL OF EVIDENCE Level III, systematic review of Level II and Level III studies and one case series.

BDNF dependence in neuroblastoma

Neuroblastomas are heterogeneous tumors arising from sympathetic precursors in the neural crest. Growth factor stimulation of neuroblastomas promote diverse biological responses (mitogenesis, differentiation, cell death) depending on the particular tumor studied. Here we show that brief treatment with retinoic acid (RA) rendered the human neuroblastoma lines SY5Y, NGP, SMS‐KCNR, and SK‐N‐SH dependent on brain‐derived neurotrophic factor (BDNF) for survival. The BDNF‐ and trkB‐expressing line SMS‐KCN was dependent on an autocrine BDNF/trkB survival without exposure to RA. We conclude that the BDNF/trkB pathway plays an important role in neuroblastoma survival and speculate on a possible role in tumor pathogenesis. J. Neurosci. Res. 64:355–363, 2001.

Medial Quadriceps Tendon–Femoral Ligament: Surgical Anatomy and Reconstruction Technique to Prevent Patella Instability

Detailed anatomic dissections of the deep medial knee retinaculum have shown a consistent prominent anatomic structure extending from the distal deep quadriceps tendon to the adductor tubercle region, forming a distinct medial quadriceps tendon-femoral ligament (MQTFL). Reconstruction of this anatomic structure has yielded consistent medial stabilization of the patellofemoral joint without drilling into the patella over more than 3 years in patients with recurrent patella instability and dislocation. Results are similar to those of MPFL reconstruction but with reduced risk of patella fracture, a known and serious complication of MPFL reconstruction. The reconstruction graft is secured at the anatomic femoral origin of the MQTFL and brought under the vastus medialis such that it may be woven and attached to the deep distal medial quadriceps tendon to provide a secure, reliable reproduction of the MQTFL and excellent stabilization of the patellofemoral joint without risk of patella fracture.

Radiographic Reference Points Are Inaccurate With and Without a True Lateral Radiograph The Importance of Anatomy in Medial Patellofemoral Ligament Reconstruction

Background: Studies have reported methods for radiographically delineating medial patellofemoral ligament (MPFL) femoral tunnel position on a true lateral knee radiograph. However, obtaining a true lateral fluoroscopic radiograph intraoperatively can be challenging, rendering radiographic methods for tunnel positioning potentially inaccurate. Purpose: To quantify the magnitude of MPFL femoral tunnel malposition that occurs on true lateral and aberrant lateral knee radiographs when using a previously reported radiographic technique for MPFL femoral tunnel localization. Study Design: Descriptive laboratory study. Methods: Ten fresh-frozen cadaveric knees were dissected to expose the MPFL femoral insertion and surrounding medial knee anatomy. True lateral and aberrant lateral knee radiographs at 2.5°, 5°, and 10° off-axis were obtained with a standard mini C-arm in 4 orientations: anterior to posterior, posterior to anterior, caudal, and cephalad. A previously reported radiographic method for MPFL femoral localization was performed on all radiographs and compared in reference to the anatomic MPFL attachment center. Results: The radiographic point, as previously described, was a mean distance of 4.1 mm from the anatomic MPFL attachment on a true lateral knee radiograph. The distance between the anatomic MPFL attachment center and the radiographic point significantly increased on aberrant lateral knee radiographs with as little as 5° of rotational error in 3 of 4 orientations of rotation when a standard mini C-arm was used. This corresponded to a malposition of 7.5, 9.2, and 8.1 mm on 5°-aberrant radiographs in the anterior-posterior, posterior-anterior, and cephalad orientations, respectively (P < .005). In the same 3 orientations of rotation, MPFL tunnel malposition on the femur exceeded 5 mm on 2.5° aberrant radiographs. Conclusion: The commonly utilized radiographic point, as previously described for MPFL femoral tunnel placement, results in inaccurate tunnel localization on a true lateral radiograph, and this inaccuracy is perpetuated with aberrant radiography. Aberrant lateral knee imaging of as little as 5° off-axis from true lateral has a significant effect on placement of a commonly used radiographic point relative to the anatomic MPFL femoral attachment center and results in nonanatomic MPFL tunnel placement. Clinical Relevance: This study demonstrates that radiographic localization of the MPFL femoral tunnel results in inaccurate tunnel placement on a true lateral radiograph, particularly when there is deviation from a true lateral fluoroscopic image, which can be difficult to obtain intraoperatively. Assessing anatomy directly intraoperatively, rather than relying solely on radiographs, may help avoid MPFL tunnel malposition.

Recurrent Anterior Shoulder Instability With Combined Bone Loss: Treatment and Results With the Modified Latarjet Procedure

Background: Recurrent anterior glenohumeral dislocation in the setting of an engaging Hill-Sachs lesion is high. The Latarjet procedure has been well described for restoring glenohumeral stability in patients with >25% glenoid bone loss. However, the treatment for patients with combined humeral head and mild (<25%) glenoid bone loss remains unclear. Purpose/Hypothesis: This study reports on the outcomes of the modified Latarjet for patients with combined humeral and glenoid defects and compares the results for patients with ≤25% glenoid bone loss versus patients with >25% glenoid bone loss. The hypothesis was that the 2 groups would have equivalent subjective outcomes and recurrence rates. Study Design: Cohort Study; Level of evidence, 3. Methods: Modified Latarjet was performed in 40 patients with recurrent anterior shoulder instability, engaging Hill-Sachs by examination confirmed with arthroscopy, and ≤25% anterior glenoid bone loss (group A). A second group of 12 patients were identified to have >25% glenoid bone loss with an engaging Hill-Sachs lesion (group B). The mean follow-up time was 3.5 years. All patients were assessed for their risk of recurrence using the Instability Severity Index score and Beighton score and had preoperative 3-dimensional imaging to assess humeral and glenoid bone loss. Single Assessment Numeric Evaluation (SANE), Western Ontario Shoulder Instability Index (WOSI), recurrence rate, radiographs, range of motion, and dynamometer strength were used to assess outcomes. A multivariate analysis was performed. Results: Glenoid bone loss averaged 15% in group A compared with 34% in group B. Both groups had comparable WOSI scores (356 vs 475; P = .311). In multivariate analysis, the number of previous surgeries and Beighton score were directly correlated with WOSI score in Latarjet patients. The SANE score was better in group A (86 vs 77; P = .02). Group B experienced more loss of external rotation (9.2° vs 15.8°; P = .0001) and weaker thumbs-down abduction and external rotation strength (P < .032). Subscapularis, abduction, and external rotation strength averaged at least 75% of the contralateral shoulder in both groups. Graft resorption was similar in both groups (32% vs 33%; P < .999). The overall recurrent instability rate for the study, defined as any subsequent subluxations or dislocation, was 15%; recurrent instability rates (15% vs 17%; P > .999) were similar for both groups. The complication rate was 25% for both groups. Conclusion: The modified Latarjet procedure provides satisfactory outcomes for patients with combined bone loss, which is known to have high recurrence rates with traditional arthroscopic stabilization. Previous surgical stabilization procedures and the Beighton score adversely affect outcome after modified Latarjet. Furthermore, the number of previous surgeries and Beighton score can be used to predict WOSI score in Latarjet patients. Further study is needed to determine if these results hold true in the long term.

Sports-related wrist and hand injuries: a review

BackgroundHand and wrist injuries are common during athletics and can have a significant impact especially if initially disregarded. Due to their high level of physical demand, athletes represent a unique subset of the population.Main bodyThe following is an overview of hand and wrist injuries commonly seen in athletics. Information regarding evaluation, diagnosis, conservative measures, and surgical treatment are provided.ConclusionKnowledge of these entities and special consideration for the athlete can help the team physician effectively treat these players and help them achieve their goals.

Osteogenic Growth Factors and Cytokines and Their Role in Bone Repair

Ontogenetic development is initiated at the time of fertilization and terminates with the differentiation, growth, and maturation of specialized tissues and organs. These developmental processes are characterized by molecular specialization that accompanies cellular differentiation and tissue morphogenesis. Most developmental processes terminate after birth or when animals reach sexual maturity, but some morphogenetic processes are reinitiated in response to injury in specific tissues. One such regenerative process is the repair of skeletal fractures and bone tissue after surgery, a process that recapitulates specific aspects of the initial developmental processes in the course of healing [58, 209]. Several aspects of the postnatal tissue environment of fracture healing, however, are unique and differ from what occurs in embryological and postnatal development.

Pectoralis Major Repair: A Biomechanical Analysis of Modern Repair Configurations Versus Traditional Repair Configuration

Background: Pectoralis major (PM) ruptures are increasingly common, and a variety of surgical techniques have been described. However, tested techniques have demonstrated diminished strength with inadequate restoration of the footprint and suture failure at relatively low loads. Purpose/Hypothesis: The purpose was to biomechanically compare PM transosseous suture repair (current gold standard) to modern PM repair techniques that use larger caliber sutures, suture tape, and unicortical button fixation (UBF). The null hypothesis was that there would be no mechanical difference between repair techniques and no difference in the amount of footprint restoration. Study Design: Controlled laboratory study. Methods: Twenty-four fresh-frozen cadaveric shoulders controlled for age and bone mineral density were randomized equally to 4 groups: (1) UBF, suture tape; (2) UBF, No. 5 suture, suture tape; (3) bone trough with No. 2 suture; and (4) native PM tendon group; all groups were tested to failure. The specimens were tested under cycling loads (10 N to 125 N) with a final load-to-failure test at 1 mm/s. Failure modes were classified by location and cause of rupture based on optical markers, while tendon footprint length was measured to determine amount of footprint restoration. Results: For fixation strength, the mean peak load was significantly greater in the native tendon (1816 ± 706 N) versus UBF/No. 5 suture/suture tape (794 ± 168 N), UBF/suture tape (502 ± 201 N), and bone trough (492 ± 151 N) (P < .001 for all). UBF/No. 5 suture/suture tape featured the lowest displacement superiorly (1.09 ± 0.47 mm) and inferiorly (1.14 ± 0.39 mm) with a significant difference compared with bone trough. With regard to tendon footprint reapproximation, cortical button fixation best approximated native tendon footprint length versus bone trough. Conclusion: Based on peak failure load, the UBF/No. 5 suture/suture tape construct demonstrated 61% greater construct strength than a traditional bone trough technique. Moreover, displacement after cyclic loading was by far smallest in the UBF/No. 5 suture/suture tape construct. Therefore, repair constructs with larger caliber suture and suture tape provide a measurable improvement in construct strength versus traditional PM repair techniques in a biomechanical model and may be advantageous for repair. Clinical Relevance: Cortical button fixation with larger caliber suture and suture tape allows for a significantly better PM repair than more traditional techniques at the time of surgery, which may ultimately result in improved clinical outcomes if implemented in surgical practice.

Is Edema at the Posterior Medial Tibial Plateau Indicative of a Ramp Lesion? An Examination of 307 Patients With Anterior Cruciate Ligament Reconstruction and Medial Meniscal Tears:

Background: Medial meniscal tears are commonly seen during anterior cruciate ligament reconstruction (ACLR). A subset of these injuries includes posterior meniscocapsular junction or “ramp” tears. One criterion that may correlate with a ramp lesion is the presence of posterior medial tibial plateau (PMTP) edema. Purpose: To compare patients with ramp lesions to patients with nonramp (meniscal body) medial meniscal tears and correlate PMTP edema on preoperative magnetic resonance imaging (MRI) to the incidence of ramp tears. Study Design: Case-control study; Level of evidence, 3. Methods: From 2006 to 2016, a total of 852 patients underwent ACLR and had operative reports available for review. Age, sex, laterality, mechanism of injury (contact/noncontact), sport, revision procedure, multiligament injury, time to MRI, and time to surgery were recorded. Preoperative MRI scans were reviewed for PMTP edema using axial, coronal, and sagittal T2 and proton-density sequences. Differences between groups were analyzed using a 2-sample t test and chi-square test. Univariate and multivariate logistic regression models examined correlations with tear type. Results: Overall, 307 patients had medial meniscal tears identified during ACLR (127 ramp lesions, 180 meniscal body lesions). The ramp group was 7.5 years younger than the meniscal body group (P < .01). The groups were not different regarding sex, contact injury, revision surgery, laterality, or multiligament injury. Patients with delayed ACLR were significantly more likely to have a meniscal body tear than a ramp lesion (odds ratio, 3.3 [95% CI, 1.9-5.6]; P < .01). The sensitivity of PMTP edema for a ramp tear was 66.3%, and 54.5% of patients with ACLR and a medial meniscal tear had PMTP edema. Patients with PMTP edema were significantly more likely to have a ramp tear than a meniscal body tear (odds ratio, 2.1 [95% CI, 1.1-4.1]; P < .03). Conclusion: The overall incidence of ramp tears in patients undergoing ACLR was 14.9%, and these tears were more prevalent in younger patients. Meniscal body tears were significantly more likely than ramp tears with delayed ACLR. In patients undergoing ACLR with an associated medial meniscal tear, the presence of PMTP edema demonstrated significantly greater odds for ramp lesions compared with meniscal body tears.