Deficiency of the collagen receptor discoidin domain receptor tyrosine kinase (DDR2) in mice and humans results in dwarfism and short limbs, of which the mechanism remains unknown. Here we report that DDR2 is a key regulator of osteoblast differentiation. DDR2 mRNA expression was increased at an early stage of induced osteoblast differentiation. In the subchondral bone of human osteoarthritic knee, DDR2 was detected in osteoblastic cells. In mouse embryos, DDR2 expression was found from E11 to E15, preceding osteocalcin (OCN) and coinciding with Runx2 expression. Activating transcription factor 4 (ATF4) enhanced DDR2 mRNA expression, and knockdown of ATF4 expression delayed DDR2 induction during osteoblast differentiation. A CCAAT/enhancer binding protein (C/EBP) binding site at À1150 bp in the DDR2 promoter was required for ATF4-mediated DDR2 activation. C/EBPb bound to and cooperated with ATF4 in stimulating DDR2 transcription; accordingly, the ATF4 mutants deficient of C/EBPb binding were incapable of transactivating DDR2. Overexpression of DDR2 increased osteoblast-specific gene expression. Conversely, knockdown of DDR2 suppressed osteogenic marker gene expression and matrix mineralization during the induced osteogenesis. The stimulation of p38 MAPK by DDR2 was required for DDR2-induced activation of Runx2 and OCN promoters. Together our findings uncover a pathway in which ATF4, by binding to C/EBPb transcriptionally upregulates DDR2 expression, and DDR2, in turn, activates Runx2 through p38 MAPK to promote osteoblast differentiation. ß

This method provides single-stage posterior decompression, correction, and stabilization on as definitive management for post traumatic kyphosis of the thoracolumbar and lumbar spine.

Medial open high tibial osteotomy (HTO) has been used to treat osteoarthritis of the medial compartment of the knee. However, weaker plate strength, unstable plate/screw junction and improper surgery technique are highly related to the HTO outcomes. Two π-shape plates were designed and eight variations (two supporting area × four locking stiffness) were compared by finite-element method. The computed tomography-based tibia was reconstructed and both wedge micromotion and implant stresses were chosen as the comparison indices. The construct was subjected to surgical and physiological loads. The medial-posterior region is the most loaded region and the load through the posterior leg is about four times that through the anterior leg. This indicates that the two-leg design can form a force-couple mechanism to effectively reduce the implant stresses. The use of locking screws significantly decrease the screw and hole stresses. However, the extending plate reduces the stresses of screws and holes above the wedge but makes the distal screws and holes much stressed. Wedge micromotion is affected by extending plate rather than locking screw. Three factors contribute to effective stabilisation of unstable HTO wedge: (1) intimate tibia-plate contact at medial-posterior regions, (2) sufficient rigidity at plate-screw junctions and (3) effective moment-balancing design at distal tibia-plate interfaces.

BackgroundHigh tibial osteotomy (HTO) with a medially opening wedge has been used to treat osteoarthritic knees. However, the osteotomized tibia becomes a highly unstable structure and necessitates the use of plate and screws to stabilize the medial opening and enhance bone healing. A T-shaped plate (e.g. TomoFix) with locking screws has been extensively used as a stabilizer of the HTO wedge. From the biomechanical viewpoint, however, the different plate sites and support bases of the HTO plate should affect the load-transferring path and wedge-stabilizing ability of the HTO construct. This study uses biomechanical tests and finite-element analyses to evaluate the placement- and base-induced effects of the HTO plates on construct performance.MethodsTest-grade synthetic tibiae are chosen as the standard specimens of the static tests. A medial wedge is created for each specimen and stabilized by three plate variations: hybrid use of T- and I-shaped plates (TIP), anteriorly placed TomoFix (APT), and medially placed TomoFix (MPT). There are five tests for each variation. The failure loads of the three constructs are measured and used as the load references of the fatigue finite-element analysis. The residual life after two hundred thousand cycles is predicted for all variations.ResultsThe testing results show no occurrence of implant back-out and breakage under all variations. However, the wedge fracture consistently occurs at the opening tip for the APT and MPT and the medially resected plateau for the TIP, respectively. The testing results reveal that both failure load and wedge stiffness of the TIP are the highest, followed by the MPT, while those of the APT are the least (P < 0.05). The fatigue analyses predict comparable values of residual life for the TIP and MPT and the highest value of damage accumulation for the APT. Both experimental and numerical tests show the biomechanical disadvantage of the APT than their counterparts. However, the TIP construct without locking screws shows the highest stress at the plate-screw interfaces.ConclusionsThis study demonstrates the significant effect of placement site and support base on the construct behaviors. The TIP provides a wider base for supporting the HTO wedge even without the use of locking screws, thus significantly enhancing construct stiffness and suppressing wedge fracture. Compared to the APT, the MPT shows performance more comparable to that of the TIP. If a single plate and a smaller incision are considered, the MPT is recommended as the better alternative for stabilizing the medial HTO wedge.

Treatment with GTN significantly increased subchondral bone thickness and density during subchondral remodelling following meniscectomy. In addition, it slightly but significantly worsened degeneration of cartilage structure and function. These results suggest that clinical use of GTN may accelerate both cartilage degeneration and subchondral bone sclerosis if used in the presence of OA, and demonstrate that NO has the potential be an important mediator of the subchondral bone changes seen in OA.