Introduction: To investigate if decreased histone deacetylase 4 (HDAC4) is associated with human osteoarthritis (OA) cartilage degeneration by releasing HDAC4 inhibition of runt-related transcription factor-2 (Runx2) resulting in increase of OA cartilage degeneration-related genes. Methods: The mRNA and protein levels of HDAC4, Runx2, matrix metalloproteinase (MMP)-13, Indian hedgehog (Ihh) and type X collagen were detected by performing real-time PCR (RT-PCR), western blotting and immunohistochemistry on specimens from human OA and normal cartilage. To further explore the mechanism of regulation of Runx2 and OA-related genes by HDAC4, changes in these OA-related genes were further quantified by RT-PCR after overexpression of HDAC4 and knockdown of HDAC4 by siRNA. Runx2 and MMP-13 promoter activities were measured by dual luciferase assays. Results: The levels of HDAC4 in the cartilage from OA patients and healthy 40- to 60-year-old donors were decreased to 31% and 65% compared with specimens from 20- to 40-year-old healthy donors, respectively (P <0.05). Decreased HDAC4 was associated with increased Runx2 and other OA-related genes in human OA cartilage, specifically: MMP-13, Ihh and type X collagen. Exogenous HDAC4 decreased the mRNA levels of Runx2, MMP1, MMP3, MMP-13, type X collagen, Ihh, ADAMTS-4 and -5, and increased the mRNA of type II collagen. In addition, the data also shows that overexpression of HDAC4 not only decreased the expression of interleukin (IL)-1β, Cox2 and iNos and increased the expression of aggrecan, but also partially blocked the effect of IL-1β on expression of catabolic events in human OA chondrocytes. HDAC4 also inhibited Runx2 promoter activity and MMP13 promotor activity in a dose-dependent manner. In contrast, inhibition of HDAC4 by TSA drug had an opposite effect. Conclusions: Our study is the first to demonstrate that decreased HDAC4 contributes, at least in part, to the pathogenesis of OA cartilage degeneration. Thus, HDAC4 may have chondroprotective properties by inhibiting Runx2 and OA-related genes.

To determine whether there is a correlation between the concentration of Indian hedgehog (Ihh) in synovial fluid (SF) and the severity of cartilage damage in the human knee joints, the knee cartilages from patients were classified using the Outer-bridge scoring system and graded using the Modified Mankin score. Expression of Ihh in cartilage and SF samples were analyzed with immunohistochemistry (IHC), western blot, and enzyme-linked immunosorbent assay (ELISA). Furthermore, we detected and compared Ihh protein levels in rat and mice cartilages between normal control and surgery-induced osteoarthritis (OA) group by IHC and fluorescence molecular tomography in vivo respectively. Ihh expression was increased 5.2-fold in OA cartilage, 3.1-fold in relative normal OA cartilage, and 1.71-fold in OA SF compared to normal control samples. The concentrations of Ihh in cartilage and SF samples was significantly increased in early-stage OA samples when compared to normal samples (r = 0.556; p < 0.001); however, there were no significant differences between normal samples and late-stage OA samples. Up-regulation of Ihh protein was also an early event in the surgery-induced OA models. Increased Ihh is associated with the severity of OA cartilage damage. Elevated Ihh content in human knee joint synovial fluid correlates with early cartilage lesions.

Objective To develop a new approach to intraoperatively identify the presence of coronal plane deformities (both valgus and varus) when treating tibial fractures with closed reduction and intramedullary nail fixation. Methods A retrospective analysis was conducted by enrolling 33 consecutive patients with tibial fractures who received closed reduction and intramedullary nail fixation from January 2018 to January 2019 at our trauma center. Out of the 33 patients, 23 were males and 10 were females and the average age was 41 years (ranging 22 to 69 years of age). Standard anteroposterior and lateral preoperative radiographs were routinely performed. After intraoperatively inserting the tibial intramedullary nail through the standard entry point, the parallel relationship between the distal horizontal interlocking screw and the tibiotalar joint surface on the anteroposterior fluoroscopy was used to determine the occurrence of valgus or varus deformities of the distal tibial fragment. Radiographic and clinical outcomes were analyzed using the average interval from injury to surgery, the lateral distal tibial angle (LDTA) of the unaffected and affected sides, complications and the Olerud–Molander ankle score. Results All 33 patients were postoperatively followed for 13 to 25 months (mean 18.7 months). The fractures achieved bone union at an average of 4.3 months (ranging from 3 to 6 months). The total complication rate was 60.6% (20 cases), including four cases that showed deep vein thrombosis, one case showing an infection and delayed union and 15 cases showing slight to moderate anterior knee pain. The postoperative LDTA of the unaffected side measured 87.3° to 89.6 ° (average 88.7° ± 0.8°), and the LDTA of the affected side was 87.5° to 90.4° (average 88.9° ± 1.1°). There was no significant difference between the unaffected and affected sides (t = −1.865, P = 0.068). The intraoperative measurement indicated six cases of valgus angulation and three cases of varus angulation deformities, and all deformities were corrected during surgery. According to the Olerud–Molander ankle score, clinical outcomes demonstrated 22 excellent cases, eight good cases, two fair cases, and one poor case 12 months after surgery. Conclusion The parallel relationship between the distal horizontal interlocking screw and tibiotalar joint surface on intraoperative anteroposterior films were able to determine the onset of valgus or varus angulations of the distal tibial fragment in the fracture zone after the tibial intramedullary nail was inserted through the standard entry point.

Objective: To design a novel blocking screws (BSs) geometry and insertion method to treat distal tibia fracture with nailing and comparison of mechanical properties of novel and traditional screws.Methods: Twenty‐one synthetic left tibiae were sectioned to obtain 21 distal segments measuring 55 mm. Intramedullary (IM) 9‐mm tibial nails were advanced to 6 mm from the ankle joint. Two transverse and one anterior–posterior (AP) locking screws were inserted. Both medial–lateral (ML) BSs were placed 10 mm from the topmost interlocking screw. A custom‐made jig assisted in placing the novel and traditional BSs. The time spent in placing each BS was recorded. All the samples were repaired with an IM nail and without BSs, with two traditional BSs, and with two novel BSs. An initial loading from −150 to +150 N was applied to specimens in the ML direction at 185 mm from the nail end, followed by cyclic loading of the same for 10,000 cycles with failure‐to‐test loading of 350 N in the ML direction. The maximum displacement was measured at 80 mm from the nail end and recorded under initial loading. The damage of two kinds of BSs to the nail was recorded.Results: Compared with average 5.21 min of the time of placing a traditional BS, the time spent in positioning a novel BS on the fracture model was 2.53 min. In the distal bone–implant constructs (BICs), the addition of traditional BSs decreased the maximum displacement of the BICs by 26.2%. The addition of the novel BSs decreased the displacement by 28.9%. All constructs survived 10,000 cycles without hardware deformation. The failure rate of the control group was significantly greater than that of the traditional group; however, the novel group was similar to the traditional group. The damage of the traditional BS to the nail was greater than that of the novel one.Conclusions: The novel and traditional BSs are comparably effective for increasing the primary mechanical stability of distal metaphyseal fractures after nailin. However, compared to the placement of a traditional BS, implanting a novel BS took more less time and caused less damage to the nail. Additionally, the most obvious advantage of the novel BS design and insertion technology was that the pressure and distance between it and the IM nail could be controlled by rotating the screw. These advantages of the novel BS will be beneficial for clinical application.

This study aims to evaluate the biomechanical performance of the Gamma 3 nail with an anti-rotation screw (GNS) and compare it to two established gold-standard methods for treating unstable femoral neck fractures (UFNFs). Synthetic bone models were prepared with Pauwels’ type III osteotomy and an additional posterior wedge. Three different implant configurations were tested: three cannulated crews (3CS) in an inverted triangle configuration, a dynamic hip screw with an anti-rotation screw (DHSS), and GNS. Non-destructive cyclic axial loading was applied at 7° adduction, with 1000 cycles ranging from 100 to 1000 N. Subsequently, a construct failure test was conducted using progressive axial compression, and fracture reduction loss was recorded. The average axial stiffness was 321 ± 52 N/mm for 3CS, 430 ± 71 N/mm for DHSS, and 519 ± 104 N/mm for GNS. The average ultimate failure loads were 2699.3 N for 3CS, 3427.1 N for DHSS, and 3758.9 N for GNS. GNS demonstrated significantly greater axial stiffness compared to the other two groups (P < 0.05). Both DHSS and GNS exhibited similar failure loading, which were greater than those of 3CS (P < 0.05). GNS offers the advantages of a minimally invasive and intramedullary implant with comparable stability to the DHSS system. Moreover, GNS demonstrated superior biomechanical performance compared to 3 CS configuration.