The increase in bone resorption and/or the inhibition of bone regeneration caused by wear particles are the main causes of periprosthetic osteolysis. The SOST gene and Sclerostin, a protein synthesized by the SOST gene, are the characteristic marker of osteocytes and regulate bone formation and resorption. We aimed to verify whether the SOST gene was involved in osteolysis induced by titanium (Ti) particles and to investigate the effects of SOST reduction on osteolysis. The results showed osteolysis on the skull surface with an increase of sclerostin levels after treated with Ti particles. Similarly, sclerostin expression in MLO‐Y4 osteocytes increased when treated with Ti particles in vitro. After reduction of SOST, local bone mineral density and bone volume increased, while number of lytic pores on the skull surface decreased and the erodibility of the skull surface was compensated. Histological analyses revealed that SOST reduction increased significantly alkaline phosphatase‐ (ALP) and osterix‐positive expression on the skull surface which promoted bone formation. ALP activity and mineralization of MC3T3‐E1 cells also increased in vitro when SOST was silenced, even if treated with Ti particles. In addition, Ti particles decreased β‐catenin expression with an increase in sclerostin levels, in vivo and in vitro. Inversely, reduction of SOST expression increased β‐catenin expression. In summary, our results suggested that reduction of SOST gene can activate the Wnt/β‐catenin signalling pathway, promoting bone formation and compensated for bone loss induced by Ti particles. Thus, this study provided new perspectives in understanding the mechanisms of periprosthetic osteolysis.

The most common cause for prosthetic revision surgery is wear particle-induced periprosthetic osteolysis, which leads to aseptic loosening of the prosthesis. Both SOST gene and its synthetic protein, sclerostin, are hallmarks of osteocytes. According to our previous findings, blocking SOST induces bone formation and protects against bone loss and deformation caused by titanium (Ti) particles by activating the Wnt/β-catenin cascade. Although SOST has been shown to influence osteoblasts, its ability to control wear-particle-induced osteolysis via targeting osteoclasts remains unclear. Mice were subjected to development of a cranial osteolysis model. Micro CT, HE staining, and TRAP staining were performed to evaluate bone loss in the mouse model. Bone marrow-derived monocyte-macrophages (BMMs) made from the C57BL/6 mice were exposed to the medium of MLO-Y4 (co-cultured with Ti particles) to transform them into osteoclasts. Bioinformatics methods were used to predict and validate the interaction among SOST, Wnt/β-catenin, RANKL/OPG, TNF-α, and IL-6. Local bone density and bone volume improved after SOST inhibition, both the number of lysis pores and the rate of skull erosion decreased. Histological research showed that β-catenin and OPG expression were markedly increased after SOST inhibition, whereas TRAP and RANKL levels were markedly decreased. In-vitro, Ti particle treatment elevated the expression of sclerostin, suppressed the expression of β-catenin, and increased the RANKL/OPG ratio in the MLO-Y4 cell line. TNF-α and IL-6 also elevated after treatment with Ti particles. The expression levels of NFATc1, CTSK, and TRAP in osteoclasts were significantly increased, and the number of positive cells for TRAP staining was increased. Additionally, the volume of bone resorption increased at the same time. In contrast, when SOST expression was inhibited in the MLO-Y4 cell line, these effects produced by Ti particles were reversed. All the results strongly show that SOST inhibition triggered the osteocyte Wnt/β-catenin signaling cascade and prevented wear particle-induced osteoclastogenesis, which might reduce periprosthetic osteolysis. Key messages: SOST is a molecular regulator in maintaining bone homeostasis. SOST plays in regulating bone homeostasis through the Wnt/β-catenin signaling pathway. SOST gene suppression stimulates osteocyte Wnt/β-catenin signaling to prevent bone resorption and attenuates particle-induced osteolysis.

Metal orthopedic implants are largely biocompatible and generally achieve long-term structural fixation. However, some orthopedic implants may loosen over time even in the absence of infection. In vivo fixation failure is multifactorial, but the fundamental biological defect is cellular dysfunction at the host-implant interface. Strategies to reduce the risk of short- and long-term loosening include surface modifications, implant metal alloy type, and adjuvant substances such as polymethylmethacrylate cement. Surface modifications (e.g., increased surface rugosity) can increase osseointegration and biological ingrowth of orthopedic implants. However, the localized responses of cells to implant surface modifications need to be better characterized. As an in vitro model for investigating cellular responses to metallic orthopedic implants, we cultured mesenchymal stromal/stem cells (MSCs) on clinical-grade titanium disks (Ti6Al4V) that differed in surface roughness as high (porous-structured), medium (grit-blasted), and low (bead-blasted). Topological characterization of clinically relevant Ti materials combined with differential mRNA expression analyses (RNA-seq and RT-qPCR) revealed alterations to the biological phenotype of cells cultured on titanium structures that favor early ECM production and observable responses to oxidative stress and heavy metal stress. These results provide a descriptive model for the interpretation of cellular responses at the interface between native host tissues and 3-D printed modular orthopedic implants, and will guide future studies aimed at increasing the long-term retention of such materials after TJA.

In glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH), downregulated osteogenic ability and damaged blood supply are two key pathogenic mechanisms. Studies suggested that cannabinoid receptor 2 (CB2) is expressed in bone tissue and it plays a positive role in osteogenesis. However, whether CB2 could enhance bone formation and blood supply in GC-induced ONFH remains unknown. In this study, we focused on the effect of CB2 in GC-induced ONFH and possible mechanisms in vitro and in vivo. By using GC-induced ONFH rat model, rat-bone mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) to address the interaction of CB2 in vitro and in vivo, we evaluate the osteogenic and angiogenic effect variation and possible mechanisms. Micro-CT, histological staining, angiography, calcein labeling, Alizarin red staining (ARS), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) staining, TUNEL staining, migration assay, scratch assay, and tube formation were applied in this study. Our results showed that selective activation of CB2 alleviates GC-induced ONFH. The activation of CB2 strengthened the osteogenic activity of BMSCs under the influence of GCs by promotion of GSK-3β/β-catenin signaling pathway. Furthermore, CB2 promoted HUVECs migration and tube-forming capacities. Our findings indicated that CB2 may serve as a rational new treatment strategy against GC-induced ONFH by osteogenesis activation and maintenance of blood supply.

There is no consensus about the optimal internal fixation selection for treatment of posterolateral tibial plateau fracture. This study described a novel plate through an anterolateral approach for posterolateral tibial plateau fractures (PTPFs). We evaluated the biomechanical performance of a novel plate and two conventional internal implants and investigated the anatomic feasibility of the novel plate. The fracture models were randomly assigned into six groups: Groups A–C were the model groups of posterolateral split fracture, fixed with the posterior buttress plate, the lateral locking plate, and the novel plate, respectively. Groups D–E were the model groups of posterolateral depression fracture, fixed with the posterior buttress plate, the lateral locking plate, and the novel plate, respectively. We evaluated the biomechanical performance of six model groups by the biomechanical testing and finite element analysis. Progressively increasing axial compressive loads were applied to each synthetic fracture model by using a customized indentor under 250–750 N loads. Meanwhile, we dissected 12 fresh frozen knee specimens and fixed them with the novel plate through the anterolateral approach. We recorded the adjacency of the novel plate to important anatomic structures. Biomechanical testing showed that the novel plate had the least displacement, followed by the posterior buttress plate, and the lateral plate had the most displacement in posterolateral split fracture. There was no significant difference in the displacement between the novel plate and the lateral plate at different loads in posterolateral depression fractures. And the posterior buttress plate showed the most displacement. In the finite element analysis, the maximum stress values of Groups A, B, and C were 383.76, 414.63, and 305.07 MPa under the load of 750 N, respectively. The maximum stress values of Groups D, E, and F were 474.28, 436.31, and 413.4 MPa under the load of 750 N, respectively. In the anatomic study, the placement of the novel plate had a low risk of damage to the important anatomic structures of knee posterolateral corner. The novel plate could be a great choice for the treatment of PTPFs due to better biomechanical performance and easy manipulation.

Background: The risks associated with deep vein thrombosis (DVT) have gained significant recognition over time. A prevalent form of distal DVT is isolated calf muscular venous thrombosis (ICMVT). Despite its common clinical occurrence, data on ICMVT subsequent to tibial plateau fracture (TPF) surgery are scarce. This study aimed to examine the epidemiological characteristics and associated risk factors (RFs) of ICMVT following TPF surgery. Methods: For this retrospective analysis, we included patients from our hospital, who underwent TPF surgery between March 2017 and March 2021. Patients’ electronic medical records were reviewed, including admission details, fracture classification, surgical procedures, and laboratory biomarkers. The HSS (The American Hospital for Special Surgery) and Rasmussen scores were employed to evaluate the clinical effect. A Color Duplex Flow Imager (CDFI) was regularly used to detect pre- and postoperative venous thrombosis in the lower limbs. Finally, uni- and multivariate logistic regression analyses were used to identify independent RFs associated with ICMVT. Results: Overall, 481 participants were recruited for analysis. Postoperative ICMVT occurred in 47 patients. All ICMVTs occurred on the affected side. Four of the 47 ICMVT patients exhibited sudden postoperative swelling in the affected limb. The HSS and Rasmussen scores in the non-ICMVT cohort (87.6 ± 8.2, 16.0 ± 1.7) were markedly different from the ICMVT cohort (84.8 ± 8.2, 15.5 ± 1.6) (p = 0.014, p = 0.031). This study finally identified five postoperative ICMVT-related RFs, which were age (> 55 years old) (OR 3.06; 95% CI 1.47–6.37; p = 0.003), gender (female) (OR 2.67; 95% CI 1.37–5.22; p = 0.004), surgical duration (> 114 min) (OR 3.14; 95% CI 1.44–6.85; p = 0.004), elevated white blood cell content (OR 2.85; 95% CI 1.47–5.51; p = 0.002), and hyponatremia (OR 2.31; 95% CI 1.04–5.12; p = 0.040). Conclusion: The epidemiological findings of this study may help predict ICMVT risk after surgery thus facilitating the development of individualized clinical assessments and targeted prevention programs.