High Tibial Osteotomy with Posterior Medial Meniscal Root Reconstruction Yields Improved Radiographic and Functional Outcomes and Healing Rates Compared to Osteotomy Alone.

PURPOSE: To compare pre- and post-operative clinical and radiological outcomes between patients undergoing high tibial osteotomy (HTO) with medial meniscus posterior root tear (MMPRT) reconstruction using gracilis tendon graft versus those without reconstruction MMPRT. METHODS: Patients with MMPRT who underwent HTO between January 2018 and December 2021 with minimum 2-year follow-up were included. All the patients were divided into 2 groups based on whether underwent meniscus root reconstruction with tendon graft, HTO alone (33 cases) and HTO with reconstruction MMPRT (21 cases). Clinical evaluation included Lysholm score, international knee documentation committee (IKDC) score, and visual analogue scale (VAS) score. The functional recovery and radiologically outcome of the knee were evaluated preoperatively and at the latest follow-up. Meniscus root healing rates and medial meniscal extrusion (MME) according to the second MRI were compared between the two groups at the latest follow-up. RESULTS: The results showed a statistically significant improvement in the postoperative Lysholm score, IKDC score, and VAS score in both groups at the latest follow-up (P<0.001). The analysis of Minimal Clinically Important Difference (MCID) for postoperative outcomes revealed that the percentage of patients who reached MCID thresholds was 100% for Lysholm, 100% for IKDC, and 100% for VAS in the HTO with reconstruction MMPRT group. In comparison, the percentages were 87.9% for Lysholm, 90.9% for IKDC, and 100% for VAS in the HTO alone group. Additionally, compared with the HTO alone group, the HTO with medial meniscus posterior root reconstruction using gracilis tendon graft significantly improved the meniscus root healing rates (Complete healing 85.7% vs. 45.4%, 95%CI: 0.003-0.007, P=0.001) and functional recovery (P<0.005 ) at the final follow-up. Additionally, the HTO with reconstruction MMPRT had a significantly better change in K-L grade (improved knees K-L grade: 10/21 vs. 6/33, P=0.033) and MME (2.1±1.0mm vs. 3.1±1.6mm, 95%CI: 0.3-1.7, P=0.007) compared to the HTO alone group. CONCLUSIONS: HTO with reconstruction of the meniscal root using a tendon graft resulted in improved radiographic and patient-reported outcomes as well as improved healing rates compared to the HTO alone.

Risk factors of incomplete healing following medial meniscus posterior root tear repair with gracilis tendon.

To evaluate the clinical efficacy and meniscus healing rates of the arthroscopically assisted tendon graft fixation of the medial meniscus posterior root tears (MMPRTs), and to identify some independent risk factors correlated with meniscal root healing status. We conducted a retrospective study with 129 patients who received arthroscopically assisted tendon graft fixation of the MMPRTs between January 2018 and September 2021. Functional recovery of the knee was evaluated and meniscal root healing status was assessed. The associations between different clinical factors and meniscal root healing status were analyzed. 98 (76.0%) patients had complete meniscal root healing with a minimum 2-year follow-up, and the Lysholm score, international knee documentation committee score, and visual analogue scale score were significantly improved at final follow-up (P < 0.001; respectively). Binary logistic regression models analysis and the receiver operating characteristic curve was performed to detect independent risk factors for incomplete healing, and these results indicated that age (OR = 1.095, P = 0.039), body mass index (BMI) (OR = 1.259, P = 0.018), preoperative meniscus extrusion (OR = 5.181, P < 0.001) and varus degree (OR = 7.764, P < 0.001) were the independent risk factors correlated with incomplete healing in patients with repaired MMPRTs. In conclusion, the arthroscopically assisted tendon graft fixation of the MMPRTs can provide good clinical and radiological outcome. Additionally, we identified age > 37.5 years, BMI > 24.5 kg/m2, preoperative meniscus extrusion > 2.7 mm and varus degree > 3.3° as independent risk factors correlated with incomplete meniscus root healing status.

Younger patients, lower BMI, complete meniscus root healing, lower HKA degree and shorter preoperative symptom duration were the independent risk factors correlated with the good correction of MME in patients with repaired MMPRTs.

PURPOSE: To evaluate the clinical and radiological outcomes of arthroscopically assisted tendon graft anatomic reinforced reconstruction of the medial meniscus posterior root tears (MMPRTs) and identify relevant factors affecting the correction of medial meniscal extrusion (MME). METHODS: Fifty-three MMPRTs patients who underwent arthroscopically assisted tendon graft reconstruction of the meniscal root between 2018 and 2020 were evaluated retrospectively. the patients were divided into 2 groups according to the correction of MME (maintained MME group: 32 cases vs. increased MME group: 21 cases). The clinical and radiological outcomes of arthroscopically assisted tendon graft reconstruction of the meniscal root, including postoperative correction of MME and functional recovery of the knee were assessed in this study, and potential independent risk factors that could influence the correction of MME were also evaluated. RESULTS: The functional recovery of the knee was significantly improved at the end of follow-up (P < 0.001; respectively), furthermore, a comparison of the final functional outcomes between the groups showed that the mean Lysholm score and IKDC score of the maintained MME group were significantly improved than those of increased MME group. 60.4% had good correction of MME, and patients with complete healing had better extrusion correction than those with partial healing and non-healing. Binary logistic regression models analysis indicated that the age (OR = 1.053, P = 0.048), BMI (OR = 1.376, P = 0.004), meniscus root healing status (OR = 7.701, P = 0.005), HKA degree (OR = 1.891, P = 0.011) and preoperative symptom duration (OR = 1.055, P = 0.013) were the independent risk factors correlated with correction of MME. Additionally, the ROC curve demonstrated the cut-off values of the Age, BMI, HKA degree and preoperative symptom duration were 46.0 years, 22.5 kg/m2, 3.2° and 9.5 months, respectively, CONCLUSIONS: The arthroscopically assisted tendon graft anatomic reinforced reconstruction of the meniscal root showed clinical improvement and prevented the progression of postoperative MME. Additionally, younger patients, lower BMI, complete meniscus root healing, lower HKA degree and shorter preoperative symptom duration were the independent risk factors correlated with the good correction of MME in patients with repaired MMPRTs. LEVEL OF EVIDENCE: Level IV.

Re-evaluating the necessity of routine laboratory tests after high tibial osteotomy surgery.

BACKGROUND: To assess the utility of routine postoperative laboratory tests for patients undergoing high tibial osteotomy (HTO) surgery. METHODS: The associations between clinical risk factors and postoperative clinical treatment were analyzed. Additionally, a logistic regression analysis was performed to detect independent risk factors for patients requiring postoperative clinical treatment. RESULTS: A total of 482 patients with symptomatic isolated medial compartment osteoarthritis from January 2015 to May 2020 were included in the present study and underwent examination by the full set of postoperative laboratory tests within 3 days after HTO surgery. However, only a small proportion of the patients with anemia (3.9 %), hypoalbuminemia (4.1 %), and abnormal serum potassium levels (3.5 %) required clinical intervention after surgery. Binary logistic regression analysis showed that the body mass index (BMI), preoperative hemoglobin level, estimated blood loss and operative duration were independent risk factors for postoperative blood transfusion in patients who underwent HTO surgery, and factors associated with albumin supplementation were female sex and preoperative albumin level. In addition, these results indicated that preoperative potassium was potential risk factor for patients who required potassium supplementation postoperatively. CONCLUSIONS: Based on the analysis, we conclude that routinely ordering postoperative laboratory tests after HTO surgery is unnecessary. However, for patients with identified risk factors, routine postoperative laboratory tests are still needed.

The risk factors for early conversion to total knee arthroplasty after high tibial osteotomy.

The primary aim was to identify potential risk factors for early conversion to total knee arthroplasty (TKA) in patients with high tibial osteotomy (HTO) surgery. A retrospective study was conducted and 240 patients received HTO surgery between January 2008 and January 2014 were included in this study. The associations between different clinical factors and HTO survivorship were analyzed. A logistic regression analysis was performed to detect independent risk factors for HTO survivorship. The cut-off value, sensitivity and specificity of these independent factors were calculated by receiver operating characteristic (ROC) curve. In this study, thirty-five (14.6%) patients were early conversion to TKA within a 5-year follow-up. These results indicated that age, body mass index (BMI), preoperative Kellgren-Lawrence (K-L) grade and preoperative visual analogue scale (VAS) score were potential risk factors for HTO survivorship. The cut-off values of those factors were 60 years, 25.35 kg/m2, 2 and 5, respectively. The combination of age, BMI, preoperative K-L grade and preoperative VAS score has the highest predictive value for HTO survivorship (AUC = 0.896, P < 0.001). Based on the present study, the five-year HTO survivorship for the treatment of medial compartment osteoarthritis of the knee was approximately 85.4%. We identified age >60 years, BMI >25.35 kg/m2, preoperative K-L grade >2 and preoperative VAS score >5 as independent risk factors for early conversion to TKA in patients with HTO surgery, and those factors combined had the highest predictive value for predicting early conversion to TKA.

Circular RNA cir-ITCH Promotes Osteosarcoma Migration and Invasion through cir-ITCH/miR-7/EGFR Pathway.

Recent studies have suggested that circular RNAs play an important role in the progression of various cancers. We aimed to investigate the possible role of cir-ITCH in osteosarcoma. In this study, we performed experiments with the human osteoblast cell line hFOB1.19 and several osteosarcoma cancer cell lines and the results showed that the expression of cir-ITCH in osteosarcoma cancer cell lines was significantly upregulated compared to that in the human osteoblast cell line. In addition, the results showed that cir-ITCH could promote the migration, invasion, and growth of osteosarcoma cells. Further mechanistic studies revealed that cir-ITCH could enhance epidermal growth factor receptor (EGFR) expression by reducing the level of miR-7. Increased EGFR phosphorylation was found to be concomitant with high expression of EGFR. We determined that cir-ITCH-mediated increase in the migration and invasion of osteosarcoma cells was dependent on EGFR phosphorylation. In conclusion, our research uncovered an important role of the cir-ITCH/miR-7/EGFR pathway in the migration and invasion of osteosarcoma cells and suggested that cir-ITCH may be a prognostic marker and a promising therapeutic target for osteosarcoma.

Arctigenin promotes bone formation involving PI3K/Akt/PPARγ signaling pathway.

This study investigated the mechanisms through which arctigenin promotes osteogenesis. Bone marrow mesenchymal stem cells (BMSCs) from ovariectomized (OVX) rats were differentiated into osteoblasts, and osteogenesis was evaluated via Alizarin Red S (ARS) staining and alkaline phosphatase (ALP) measurements in cultured BMSCs. The levels of phosphorylated AKT serine/threonine kinase 1 (p-Akt), and peroxisome proliferator-activated receptor gamma (PPARγ) expression were quantified by Western blot analysis. The levels of urine calcium (U-Ca), urine phosphorus (U-P), serum ALP, and bone mineral density (BMD) of OVX rats were assessed in vivo. The results showed that treatment with arctigenin in rat BMSCs enhanced mineralization, increased ALP activity, increased the expression of Akt and p-Akt, and decreased PPARγ expression, consistent with its ability to promote osteoblast differentiation. Furthermore, arctigenin prevented OVX-induced osteoporosis in rats by increasing BMD and ALP activity and inhibiting the loss of Ca and P. In contrast, treatment with LY294002, a selective inhibitor of the phosphatidylinositol 3-kinase (PI3K), produced the opposite phenotype. These data suggest that the protective effects of arctigenin on BMSCs and OVX rat models result from the induction of osteogenesis involving the PI3K/Akt/PPARγ axis.

The mechanism research of non-Smad dependent TAK1 signaling pathway in the treatment of bone defects by recombination BMP-2-loaded hollow hydroxyapatite microspheres/chitosan composite.

AIMS: The present study aimed to evaluate whether the non-Smad dependent TAK1 signaling pathway (BMP-2-TAK1-p38-Osx signaling pathway) played an important role in bone repair mediated by hollow hydroxyapatite (HA) microspheres/chitosan (CS) composite. METHODS: Firstly, the biological activity of rhBMP-2 released from the complex was investigated. Then, differentiation test of osteoblasts including ALP activity and calcium deposition, X-ray scoring and three-point bending test were performed. Finally, the mRNAs expression of TAK1, p38, Osx and osteogenic markers was tested by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: RhBMP-2 could be loaded and released from the complex in bioactive form. Additionally, the complex provided a prolonged period of time compared with HA/CS scaffolds. Serum ALP activity was significantly decreased in the TAK1 inhibitor group and p38 inhibitor group. In the X-ray radiography, bone callus was observed in rhBMP-2-loaded hollow HA microspheres/CS composite group. In the three-point bending test, load values in p38 inhibitor group decreased. In the animal model, the mRNA expression of BSP on day 90 was significantly decreased in the p38 inhibitor group and TAK1 inhibitor group. In MC3T3-E1 cells, the mRNA expression of OSX was remarkably up-regulated in both rhBMP-2 group or rhBMP-2-loaded hollow HA microspheres/CS composite group; while the mRNA expression of OSX was significantly down-regulated in TAK1 inhibitor group and p38 inhibitor group. CONCLUSION: The BMP-2-TAK1-p38-OSX signaling pathway may play an important role in bone formation and repair mediated by rhBMP-2-loaded hollow HA microspheres/CS composite.

Study of bone repair mediated by recombination BMP-2/ recombination CXC chemokine Ligand-13-loaded hollow hydroxyapatite microspheres/chitosan composite.

AIMS: The present study aimed to investigate the mechanism of bone repair mediated by recombination BMP-2 (rhBMP-2)/recombination CXC chemokine ligand-13 (rhCXCL13)-loaded hollow hydroxyapatite (HA) microspheres/chitosan (CS) composite. MATERIALS AND METHODS: Firstly, the biological activity of rhBMP-2 and rhCXCL13 released from the complex was investigated. Secondly, the effect of rhBMP-2 sustained release solution on ALP activity and rhCXCL13 sustained release solution on cell migration of rat bone marrow mesenchyme stem cells was tested. Thirdly, osteoblasts differentiation test, X-ray scoring and three-point bending test were performed. Finally, the mRNAs expression of osteogenic marker genes and the protein expression of Runx2 was tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting (WB), respectively. KEY FINDINGS: RhBMP-2 could significantly promote the proliferation and differentiation, and RhCXCL13 could promote the migration of rat bone marrow MSCs. Detection of ALP activity and calcium salt deposition showed that rhBMP-2 and rhCXCL13 could significantly improve the biological activity and promote cell differentiation ability. X-ray scoring of radius and flexural strength test showed that rhBMP-2 and rhCXCL13 could promote bone healing and improve the bending resistance of bone tissue. The in vitro molecular experiments including RT-PCR and WB further demonstrated the roles of rhBMP-2 and rhCXCL13 in bone formation and bone repair. SIGNIFICANCE: Our results indicated that the hollow HA microspheres/CS composite could be effective as a delivery vehicle for rhBMP-2 and rhCXCL13 in bone regeneration and bone repair. In this process, rhBMP-2 may promote bone regeneration by regulating bone marrow MSCs cells recruited by rhCXCL13.

Scaffolds for the repair of bone defects in clinical studies: a systematic review.

BACKGROUND: This systematic review aims to summarize the clinical studies on the use of scaffolds in the repair of bony defects. METHODS: The relevant articles were searched through PubMed database. The following keywords and search terms were used: "scaffolds," "patient," "clinic," "bone repair," "bone regeneration," "repairing bone defect," "repair of bone," "osteanagenesis," "osteanaphysis," and "osteoanagenesis." The articles were screened according to inclusion and exclusion criteria, performed by two reviewers. RESULTS: A total of 373 articles were obtained using PubMed database. After screening, 20 articles were identified as relevant for the purpose of this systematic review. We collected the data of biological scaffolds and synthetic scaffolds. There are eight clinical studies of biological scaffolds included collagen, gelatin, and cellular scaffolds for bone healing. In addition, 12 clinical studies of synthetic scaffolds on HAp, TCP, bonelike, and their complex scaffolds for repairing bone defects were involved in this systematic review. CONCLUSIONS: There are a lot of clinical evidences showed that application of scaffolds had a good ability to facilitate bone repair and osteogenesis. However, the ideal and reliable guidelines are insufficiently applied and the number and quality of studies in this field remain to be improved.

[Chondrogenic phenotype differentiation of bone marrow mesenchymal stem cells induced by bone morphogenetic protein 2 under hypoxic microenvironment in vitro].

OBJECTIVE: To investigate the role of bone morphogenetic protein 2 (BMP-2) combined with hypoxic microenvironment in chondrogenic phenotype differentiation of bone marrow mesenchymal stem cells (BMSCs) of rat in vitro. METHODS: BMSCs were harvested from 4-week-old female Sprague Dawley rats. BMSCs at passage 2 were divided into 4 groups according different culture conditions: normoxia control group (group A), normoxia and BMP-2 group (group B), hypoxia control group (3% oxygen, group C), and hypoxia and BMP-2 group (group D). Then the cellular morphology was observed under inverted phase contrast microscope. Alcian blue immunohistochemical staining was used to detect the glycosaminoglycans (GAG), Western blot to detect collagen type II and hypoxia-inducible factor 1alpha (HIF-1alpha), and RT-PCR to detect the expressions of chondrogenic related genes, osteogenic related genes, and hypoxia related genes. RESULTS: At 21 days after induction of BMP-2 and hypoxia (group D), BMSCs became round, cell density was significantly reduced, and lacuna-like cells were wrapped in cell matrix, while the changes were not observed in groups A, B, and C. Alcian blue staining in group D was significantly bluer than that in other groups, and staining became darker with induction time, and the cells were stained into pieces of deeply-stained blue at 21 days. Light staining was observed in the other groups at each time point. The expression level of collagen type II protein in group D was significantly higher than those in other groups (P < 0.05). HIF-1alpha protein expression levels of groups C and D were significantly higher than those of groups A and B (P < 0.05). The expressions of collagen II alpha1 (COL2 alpha1) and aggrecan mRNA (chondrogenic related genes) were highest in group D, while the expressions of COL1 alpha1, alkaline phosphatase, and runt-related transcription factor 2 mRNA (osteogenic related genes) were the highest in group B (P < 0.05). Compared with groups A and B, HIF-1alpha (hypoxic related genes) in groups C and D significantly increased (P < 0.05). CONCLUSION: BMP-2 combined with hypoxia can induce differentiation of BMSCs into the chondrogenic phenotype, and inhibit osteoblast phenotype differentiation. HIF-1alpha is an important signaling molecule which is involved in the possible mechanism to promote chondrogenic differentiation process.

Chlorogenic acid protects MSCs against oxidative stress by altering FOXO family genes and activating intrinsic pathway.

Chlorogenic acid as an antioxidant exists widely in edible and medicinal plants, and can protect cell against apoptosis induced by oxidative stress. However, its molecular mechanisms remain largely unknown. Here, we showed that Chlorogenic acid suppressed reactive oxygen species increase by activation of Akt phosphorylation,and increased FOXO family genes and anti-apoptotic protein Bcl-2 expression in MSCs culturing under oxidative stress. In addition, PI-3Kinase Inhibitor (2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, LY294002) could suppress the Chlorogenic acid-induced: (1) the cellular protective role, (2) the increase of the FOXO family genes expression, (3) increased expression of Bcl-2. These results suggested that Chlorogenic acid protected MSCs against apoptosis via PI3K/AKT signal and FOXO family genes.