Peihui Wu

The biomechanical differences of rotational acetabular osteotomy, Chiari osteotomy and shelf procedure in developmental dysplasia of hip

BackgroundRotational acetabular osteotomy (RAO), Chiari osteotomy and shelf procedure are important treatments to delay the progression of osteoarthritis in developmental dysplasia of hip (DDH) patients, but their biomechanical differences are still unknown. This study was to evaluate the different biomechanical changes of hip joint after these three surgeries.MethodsSixteen DDH models of 8 human cadaver specimens were reconstructed, and treated by different surgeries, and then strain around femoral head was evaluated by strain gauges.ResultsHip strain value of DDH model was decreased after treated by shelf procedure (Pleft = 0.016 and Pright = 0.021) and rotational acetabular osteotomy (P = 0.004), but not in Chiari osteotomy (P = 0.856). Moreover, the improved ratio of RAO treatment was better than shelf procedure (P = 0.015) and Chiari osteotomy (P = 0.0007), and the descendent range of shelf procedure was greater than Chiari osteotomy (P = 0.018).ConclusionsFrom biomechanics points, RAO was more effective in relieving hip joint stress compared with shelf procedure and Chiari osteotomy.

Presence and function of microRNA-92a in chondrogenic ATDC5 and adipose-derived mesenchymal stem cells

The aim of the present study was to investigate the presence and biological function of microRNA-92a (miR-92a) in chondrogenesis and cartilage degeneration. Human adipose-derived mesenchymal stem cells (hADSCs) in micromass and chondrocyte-like ATDC5 cells were induced to chondrogenesis, and primary human/mouse chondrocytes (PHCs/PMCs) and chondrogenic ATDC5 cells were stimulated with interleukin-1β (IL-1β). An miR-92a mimic/inhibitor was transfected into the ATDC5 cells using lipofectamine 2000. Gene expression was analyzed using reverse transcription-quantitative polymerase chain reaction. Alcian blue was used to stain the cartilage nodules and chondrogenic micromass. The potential target genes, signaling pathways and functions of miR-92a were examined using miRanda, miRDB, CLIP-Seq, TargetScan and Kyoto Encyclopedia of Genes and Genomes. The expression of miR-92a was elevated in the chondrogenic ATDC5 cells and hADSCs, and also in the IL-1β-induced ATDC5 cells, PMCs and PHCs. Forced expression of miR-92a enhanced the expression levels of col9a2 and aggrecan. A total of 279 genes were predicted as potential target genes of miR-92a. The phosphoinositide 3-kinase/PI3K)-Akt, ErbB and focal adhesion kinase pathways, extracellular matrix (ECM)-receptor interaction and the mammalian target of rapamycin (mTOR) signaling pathway were suggested to mediate the effects of miR-92a on chondrogenesis and cartilage degeneration. These results demonstrated that miR-92a was involved in chondrogenesis and the chondrocyte response induced by IL-1β. miR-92a positively contributed to the expression of col9a2 and of aggrecan.

MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

Background/Aims: Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) are secreted enzymes belonging to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family that play significant roles in the progression of osteoarthritis (OA). Here, we aimed to determine whether the expression of ADAMTS-4/5 in chondrogenesis and inflammation is regulated by microRNA-92a-3p (miR-92a-3p). Methods: MiR-92a-3p and ADAMTS-4/5 expressions were determined by quantitative polymerase chain reaction (qPCR). To investigate the repressive effect of miR-92a-3p on ADAMTS-4/5 expression, chondrogenic human mesenchymal stem cells (hMSCs) and human chondrocytes were transfected with mature miR-92a-3p or an antisense inhibitor (anti-miR-92a-3p), respectively. ADAMTS-4/5 protein production was quantified by enzyme-linked immunosorbent assay (ELISA), and miR-92a-3p involvement in IL-1β-mediated catabolic effects was examined by immunoblotting. The roles of activated MAP kinases (MAPK) and nuclear factor (NF)-κB were evaluated by using specific inhibitors. Interaction between miR-92a-3p and its putative binding site in the 3′-untranslated region (3′-UTR) of ADAMTS-4/5 mRNA was confirmed by luciferase reporter assay. Results: miR-92a-3p expression was elevated in chondrogenic hMSCs, with significantly lower expression in OA cartilage than in normal cartilage. Stimulation with IL-1β significantly reduced miR-92a-3p expression in primary human chondrocytes (PHCs). Transfection of chondrocytes with miR-92a-3p downregulated IL-1β-induced ADAMTS-4/5 expression, and the activity of a reporter construct containing the 3′-UTR of human ADAMTS-4/5 mRNA. MiR-92a-3p expression was suppressed upon IL-1β-induced activation of MAPK and NF-κB in chondrocytes. Conclusion: MiR-92a-3p is an important regulator of ADAMTS-4/5 in human chondrocytes and may contribute to the development of OA.

MicroRNA-193b-3p regulates chondrogenesis and chondrocyte metabolism by targeting HDAC3

Histone deacetylase 3 (HDAC3) plays a pivotal role in the repression of cartilage-specific gene expression in human chondrocytes. The aim of this study was to determine whether microRNA-193b-3p (miR-193b-3p) regulates the expression of HDAC3 during chondrogenesis and chondrocyte metabolism. Methods: miR-193b-3p expression was assessed in a human mesenchymal stem cell (hMSC) model of chondrogenesis, in interleukin-1β (IL-1β)-treated primary human chondrocytes (PHCs), and in non-degraded and degraded cartilage. hMSCs and PHCs were transfected with miR-193b-3p or its antisense inhibitor. A direct interaction between miR-193b-3p and its putative binding site in the 3′-untranslated region (3′-UTR) of HDAC3 mRNA was confirmed by performing luciferase reporter assays. Chondrocytes were transfected with miR-193b-3p before performing a chromatin immunoprecipitation assay with an anti-acetylated histone H3 antibody. To investigate miR-193b-3p-transfected PHCs in vivo, they were seeded in tricalcium phosphate-collagen-hyaluronate (TCP-COL-HA) scaffolds, which were then implanted in nude mice. In addition, plasma exosomal miR-193b-3p in samples from normal controls and patients with osteoarthritis (OA) were measured. Results: miR-193b-3p expression was elevated in chondrogenic and hypertrophic hMSCs, while expression was significantly reduced in degraded cartilage compared to non-degraded cartilage. In addition, miR-193b-3p suppressed the activity of reporter constructs containing the 3′-UTR of HDAC3, inhibited HDAC3 expression, and promoted histone H3 acetylation in the COL2A1, AGGRECAN, COMP, and SOX9 promoters. Treatment with the HDAC inhibitor trichostatin A (TSA) increased cartilage-specific gene expression and enhanced hMSCs chondrogenesis. TSA also increased AGGRECAN expression and decreased MMP13 expression in IL-1β-treated PHCs. Further, 8 weeks after implanting PHC-seeded TCP-COL-HA scaffolds subcutaneously in nude mice, we found that miR-193b overexpression strongly enhanced in vivo cartilage formation compared to that found under control conditions. We also found that patients with OA had lower plasma exosomal miR-193b levels than control subjects. Conclusions: These findings indicate that miR-193b-3p directly targets HDAC3, promotes H3 acetylation, and regulates hMSC chondrogenesis and metabolism in PHCs.

Value of Computed Tomography-Based Three-Dimensional Pre-operative Planning in Cup Placement in Total Hip Arthroplasty With Dysplastic Acetabulum

Abstract Objects: To investigate the value of CT-based 3D templating software for pre-operative planning in patients with acetabular dysplasia undergoing total hip arthroplasty (THA) with a minimum follow-up of 2 years. Methods: We performed a retrospective review of a single surgeon’s cohort of patients with Crowe I to III developmental dysplastic hip (49 hips in 41 patients) who underwent cementless primary THA and were available for follow-up at a mean of 2.7 years after THA. We analyzed the accuracy of cup size prediction, the reliability of pre- and post-operative cup orientation and position of reconstructed rotation center using CT-based 3D templating software. Post-operative Harris Hip Score and lower limb discrepancy was obtained at the last follow-up. Results: The sizes of 71% of the cup components (35/49) were estimated exactly, and 100% of the cup size estimates were accurate to within one-cup size. There was good reproducibility of pre- and post-operative position of reconstructed rotation center (correlation coefficient r = 0.396 for vertical position, p = 0.005; r = 0.326 for horizontal position, p = 0.024). There was no substantial agreement between the planned acetabular orientation and that measured post-operatively (correlation coefficient –0.174 for inclination and 0.045 for anteversion). There were 44 (90%) excellent or good results according to HHS. Seven patients (14%) reported lower limb discrepancy. Conclusions: Pre-operative CT-based 3D templating made it possible to predict accurate cup size and achieve reproducible cup position in patients with dysplastic acetabulum. The reproducibility of cup orientation could not be demonstrated in this study.

Exosomal miR-95-5p regulates chondrogenesis and cartilage degradation via histone deacetylase 2/8

Abstract MicroRNAs play critical roles in the pathogenesis of osteoarthritis, the most common chronic degenerative joint disease. Exosomes derived from miR‐95‐5p‐overexpressing primary chondrocytes (AC‐miR‐95‐5p) may be effective in treating osteoarthritis. Increased expression of HDAC2/8 occurs in the tissues and chondrocyte‐secreted exosomes of patients with osteoarthritis and mediates cartilage‐specific gene expression in chondrocytes. We have been suggested that exosomes derived from AC‐miR‐95‐5p (AC‐miR‐95‐5p‐Exos) would enhance chondrogenesis and prevent the development of osteoarthritis by directly targeting HDAC2/8. Our in vitro experiments showed that miR‐95‐5p expression was significantly lower in osteoarthritic chondrocyte‐secreted exosomes than in normal cartilage. Treatment with AC‐miR‐95‐5p‐Exos promoted cartilage development and cartilage matrix expression in mesenchymal stem cells induced to undergo chondrogenesis and chondrocytes, respectively. In contrast, co‐culture with exosomes derived from chondrocytes transfected with an antisense inhibitor of miR‐95‐5p (AC‐anti‐miR‐95‐5p‐Exos) prevented chondrogenic differentiation and reduced cartilage matrix synthesis by enhancing the expression of HDAC2/8. MiR‐95‐5p suppressed the activity of reporter constructs containing the 3ʹ‐untranslated region of HDAC2/8, inhibited HDAC2/8 expression and promoted cartilage matrix expression. Our results suggest that AC‐miR‐95‐5p‐Exos regulate cartilage development and homoeostasis by directly targeting HDAC2/8. Thus, AC‐miR‐95‐5p‐Exos may act as an HDAC2/8 inhibitor and exhibit potential as a disease‐modifying osteoarthritis drug.

Better Prognosis of Senile Patients with Intertrochanteric Femoral Fracture by Treatment with Open Reduction Internal Fixation than by Hip Arthroplasty

ABSTRACT Purpose: To compare the postoperative survival and mortality rates in intertrochanteric femoral fracture (IFF) patients who underwent either open reduction internal fixation (ORIF) or hip arthroplasty. Methods: Clinical data from senior patients who had IFF and underwent ORIF or hip arthroplasty were analyzed retrospectively. Survival curves were compared between groups with Kaplan–Meier method and log-rank test. Significant independent prognostic factors were identified by Cox multivariate regression analysis. Results: All patients recovered fully post-surgery. Although 31 patients died during the follow-up period (ORIF, mean 45.4 months; arthroplasty, mean 51.6 months), mortality rate did not differ significantly between the groups. The 1-yr and 2-yr survival rate estimates for the ORIF group were 92.2%, and 86%, respectively; they were 85% and 74% for the arthroplasty group. Average survival lengths for ORIF and arthroplasty groups were 88 and 67 months, respectively. The effect of surgical approaches on survival differed significantly (log-rank test c2 = 6.402, p = 0.011). Multivariate Cox regression model indicated that surgical choice (p = 0.036) was a significant independent risk factor for the prognosis of senile IFF, even with adjustment for age (p = 0.002). Conclusion: The overall postoperative prognosis was superior in senile IFF patients treated with ORIF.

Radiographic Measurement of Femoral Lateral Bowing and Distal Femoral Condyle Resection Thickness: Variances and Effects on Total Knee Arthroplasty Planning

Background: Accurate evaluation of the plain radiography of lower limb is critical for preoperative planning of total knee arthroplasty (TKA). We aimed to investigate the effect of femoral lateral bowing and rotation on the radiographic measurements of distal femoral condyle resection thickness (DRT) and the distal femoral resection valgus angle (FVA). Methods: We analyzed 246 three-dimensional femoral models generated from computed tomography images of 123 patients, acquiring projected contours in seven positions – 20° and 10° internal rotation; 0° rotation; 10°, 20°, 30°, and 40° external rotation – for each model. Medial and lateral condyle DRTs, femoral shaft lateral bowing angle (FBA), and distal FVA were determined for each position. Linear mixed effect model was used to determine the effect of degree of femur rotation on repeated measurements of DRT or FVA. Results: FBA significantly affected the FVA and DRT (Pearsons R = 0.767 and −0.408, respectively; P < 0.000). Samples were divided into three groups according to the FBA measured in neutral position: FBA <0°: DRT 3.75 ± 1.30 mm, FVA 4.53° ± 1.27°; FBA >0° but <3°: DRT 3.39 ± 1.31 mm, FVA 5.92° ± 1.31°; FBA >3°: DRT 2.22 ± 1.31 mm, FVA 7.37° ± 1.31°. From simulated 20° internal rotation to 40° external rotation in each femoral model, the average variation ranges of radiographically measured DRT, FVA, and FBA were 0.50 ± 0.28 mm, 2.93° ± 0.96°, and 10.33° ± 1.90°, respectively, with no significant differences among the FBA groups. The degree of femoral rotation significantly affected the FVA (F = 62.148, P < 0.000), whereas there was no effect on condyle resection thickness (F = 0.4705, P = 0.494). Conclusions: Axial femoral rotation has less effect on radiographic measurements of differences in the DRT than on those of the distal FVA.

Preoperative Measurement of Tibial Resection in Total Knee Arthroplasty Improves Accuracy of Postoperative Limb Alignment Restoration

Background:Accuracy of implant placement in total knee arthroplasty (TKA) is crucial. Traditional extramedullary alignment instruments are fairly effective for achieving the desired mean tibial component coronal alignment. We modified the traditional tibial plateau resection technique and evaluated its effect on alignment restoration. Methods:Two hundred and eighty-two primary TKAs in our hospital between January 2013 and December 2014 were enrolled in this retrospective study. Group A consisted of 128 primary TKAs performed by one senior surgeon. Preoperative measurement of the tibial resection was conducted on radiographs, and the measured thicknesses of the lateral and medial plateau resection were used to place the tibial alignment guide. Group B consisted of 154 primary TKAs performed by the other senior surgeon, using a traditional tibial plateau resection technique. In all patients, an extramedullary guide was used for tibial resection, and preoperative and postoperative full-leg standing radiographs were used to assess the hip-knee-ankle angle (HKA), femoral component alignment angle (FA), and tibial component alignment angle (TA). A deviation ≥3° was considered unsatisfactory. Data were analyzed by unpaired Students t-test. Results:The mean postoperative HKA and TA angles were significantly different between Groups A and B (178.2 ± 3.2° vs. 177.0 ± 3.0°, t = 2.54, P = 0.01; 89.3 ± 1.8° vs. 88.3 ± 2.0°, t = 3.75, P = 0.00, respectively). The mean postoperative FA was 88.9 ± 2.5° in Group A and 88.9 ± 2.6° in Group B, and no significant difference was detected (t = 0.10, P = 0.92). There were 90 (70.3%) limbs with restoration of the mechanical axis to within 3° of neutral alignment and 38 (29.7%) outliers (>3° deviation) in Group A, whereas there were 89 (57.8%) limbs with restoration of the mechanical axis to within 3° of neutral alignment and 65 (42.2%) outliers (>3° deviation) in Group B. The severity of the preoperative alignment deformity was a strong predictor for postoperative alignment. Conclusions:Using conventional surgical instruments, preoperative measurement of resection thickness of the tibial plateau on radiographs could improve the accuracy of conventional surgical techniques.

Impaired ossification coupled with accelerated cartilage degeneration in developmental dysplasia of the hip: evidences from μCT arthrography in a rat model

BackgroundDevelopmental dysplasia of the hip (DDH) always leads to cartilage degeneration and osteoarthritis of the hip joint. However, the diagnosis of early cartilage degeneration in DDH is still a clinical challenge. This study aims to investigate the dynamic changes of bone and cartilage in the hip of a rat model of DDH and to explore the potential application of microcomputed tomography (μCT) arthrography to detect early cartilage degeneration in DDH.MethodsNewborn Wistar rats were used to induce DDH by hindlimb swaddling. The bone and cartilage of the hip in model and control group were analyzed by μCT arthrography and histology examination at postnatal day 10, week 4, 6 and 8.ResultsHip dysplasia developed with age, became obvious at postnatal week 6 and further progressed at week 8. μCT analysis showed that bone mineral density (BMD) and bone volume density (bone volume over total volume, BV/TV) of the femoral head and neck region (FHNR) in model group were both significantly lower than those in control group, and they increased dramatically from postnatal week 4 to week 6 but maintained at a similar level at week 8. Contrast-enhanced μCT (CE-μCT) arthrography and histology data showed age-dependent increase in cartilage attenuation (CA) and decrease in safranin O staining intensity (SI) in model group, respectively. Moreover, the model group revealed remarkably higher CA and lower SI than control group, respectively. In addition, significant changes of CA and SI were both observed from postnatal week 6 to week 8 in model group. A strong linear correlation (r2 = 0.789, P <0.001) was found between CA and SI in model group. Furthermore, BMD was negatively correlated with SI (t = -2.683, P <0.05), whereas specific bone surface (bone surface over bone volume, BS/BV) was positively correlated with SI (t =4.501, P <0.01), in model group.ConclusionsImpaired ossification coupled with continuous loss of sGAG in cartilage matrix was found in the dysplasia hip during the disease progression of DDH. Cartilage degeneration in the dysplasia hip may occur early at childhood, accelerated with age and become irreversible at young adult stage. All these abnormal changes could be quantitatively assessed by μCT arthrography.