Baoyi Liu

Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells

BACKGROUND Treatment of early-stage osteonecrosis of the femoral head (ONFH) with autologous implantation of iliac crest bone marrow-derived mononuclear cells, which contain tens of thousands of bone marrow mesenchymal stem cells (BMMSCs), recently achieved a promising outcome. METHODS One hundred patients with early-stage ONFH were recruited and randomly assigned to BMMSC treatment or core decompression (CD) treatment. Each BMMSC-treated hip received femoral head (FH) implantation of 2×10(6) autologous subtrochanteric bone marrow-derived and ex vivo expanded BMMSCs. The radiographic stage of ONFH according to the Association Research Circulation Osseous classification, Harris hip score (HHS), and the volume of the necrotic lesion or the low signal intensity zone (LowSIZ) in the FH were assessed before and 6, 12, 24, and 60 months after the initial operation. RESULTS Sixty months after the operation, only 2 of the 53 BMMSC-treated hips progressed and underwent vascularized bone grafting. In CD group, 7 hips lost follow-up, and 10 of the rest 44 hips progressed and underwent vascularized bone grafting (5 hips) or total hip replacement (5 hips). Compared with the CD group, BMMSC treatment significantly improved the HHS as well as decreased the volume of femoral head LowSIZ of the hips preoperatively classified at stage IC, IIB, and IIC (P<0.05, respectively; stage IIA, P=0.06, respectively). No complication was observed in both treatment groups. CONCLUSIONS Ex vivo expansion of autologous BMMSCs can reliably provide a greater number of BMMSCs for FH implantation. This intervention is safe and effective in delaying or avoiding FH collapse, which may necessitate total hip replacement.

Autologous Bone Marrow Mesenchymal Stem Cells Associated with Tantalum Rod Implantation and Vascularized Iliac Grafting for the Treatment of End-Stage Osteonecrosis of the Femoral Head

Tantalum rod implantation with vascularized iliac grafting has been reported to be an effective method for the treatment of young patients with osteonecrosis of the femoral head (ONFH) to avert the need for total hip arthroplasty (THA). However, there have been unsatisfactory success rates for end-stage ONFH. The authors describe a modified technique using bone marrow mesenchymal stem cells (BMMSCs) associated with porous tantalum rod implantation combined with vascularized iliac grafting for the treatment of end-stage ONFH. A total of 24 patients (31 hips) with end-stage ONFH were treated with surgery; ARCO IIIc stage was observed in 19 hips and ARCO IV stage was observed in 12 hips. All patients were followed for a mean time of 64.35 ± 13.03 months (range 26–78). Operations on only five hips were converted to THA. The joint-preserving success rate of the entire group was 89.47% for ARCO stage IIIc and 75% for ARCO stage IV. The mean Harris hip score of the 31 hips improved significantly from 38.74 ± 5.88 points (range 22–50) to 77.23 ± 14.75 points (range 33–95). This intervention was safe and effective in delaying or avoiding total hip replacement for end-stage ONFH.

Digital subtraction angiography in selection of the vascularized greater trochanter bone grafting for treatment of osteonecrosis of femoral head

The aim of this report is to present our experience on the use of the digital subtraction angiography (DSA) in selection of the vascularized greater trochanter bone grafting for the treatment of the osteonecrosis of femoral head (ONFH) in early stages. Between January 2005 and June 2007, DSA was used to evaluate the blood perfusion of the early stages ONFH in 32 patients (45 hips). There were 18 males and 14 females with an average age of 30 years old. Twenty‐one hips were in ARCO stage I, and 24 in ARCO stage II. The arterial blood supply insufficiency was found in 22 hips by DSA, and the venous stasis in 23 hips. The hips with artery blood supply insufficiency received the vascularized greater trochanter bone grafting, and the hips with the venous stasis received the core decompression. All of patients were followed‐up with an average of 4.8 years (ranging 2.4–6.6 years). The preoperative Harris Hip score (HHS) in the patients with arterial blood supply insufficiency was 48.18 ± 7.81 and the postoperative HHS was 93.27 ± 3.03. The preoperative HHS in the patients with venous stasis was 44.04 ± 6.40, and the postoperative HHS 92.65 ± 2.93. The postoperative DSA showed an improved perfusion of the femoral head in 44 hips. Our experience showed that DSA would help to select the appropriate procedure for treatment of ONFH in the early stage.

Omentin-1 prevents cartilage matrix destruction by regulating matrix metalloproteinases

Matrix metalloproteinases (MMPs) play a crucial role in the degradation of the extracellular matrix and pathological progression of osteoarthritis (OA). Omentin-1 is a newly identified anti-inflammatory adipokine. Little information regarding the protective effects of omentin-1 in OA has been reported before. In the current study, our results indicated that omentin-1 suppressed expression of MMP-1, MMP-3, and MMP-13 induced by the proinflammatory cytokine interleukin-1β (IL-1β) at both the mRNA and protein levels in human chondrocytes. Importantly, administration of omentin-1 abolished IL-1β-induced degradation of type II collagen (Col II) and aggrecan, the two major extracellular matrix components in articular cartilage, in a dose-dependent manner. Mechanistically, omentin-1 ameliorated the expression of interferon regulatory factor 1 (IRF-1) by blocking the JAK-2/STAT3 pathway. Our results indicate that omentin-1 may have a potential chondroprotective therapeutic capacity.

Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo

Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum–host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing.

Protective effects of Nebivolol against interleukin-1β (IL-1β)-induced type II collagen destruction mediated by matrix metalloproteinase-13 (MMP-13)

The pathological progression of osteoarthritis (OA) involves degradation of articular cartilage matrix. Type II collagen is the main component of cartilage matrix, which is degraded by pro-inflammatory cytokines such as IL-1β mediated by MMP-13. Nebivolol, a licensed drug used for the treatment of hypertension in clinics, displays its anti-inflammatory capacity in various conditions. However, whether Nebivolol has a protective effect on cartilage matrix degradation has not been reported before. In this study, we investigated the effects of Nebivolol on regulating the expression of MMP-13 and degradation of type II collagen. Our results indicate that Nebivolol alleviated the increase in gene expression, protein expression, and activity of MMP-13 induced by IL-1β. Importantly, IL-1β strikingly reduced the levels of type II collagen in cell culture supernatants, which was reversed by treatment with Nebivolol in a dose-dependent manner. Mechanistically, Nebivolol was found to alleviate the increased levels of phosphorylated IκBα and reduced levels of total IκBα induced by IL-1β, which subsequently mitigated p65 nuclear translocation and the transcriptional activity of NF-κB. Furthermore, our results indicated that IL-1β treatment resulted in a significant increase in expression of the transcriptional factor interferon regulatory factor-1 (IRF-1) at both the mRNA and protein levels, which was significantly ameliorated by treatment with Nebivolol. The combination of these findings suggests that Nebivolol can potentially be applied in human OA treatment.

Ion channel functional protein kinase TRPM7 regulates Mg ions to promote the osteoinduction of human osteoblast via PI3K pathway: In vitro simulation of the bone-repairing effect of Mg-based alloy implant

Mg-based alloys, as the potential orthopaedic implant, can self-degrade to avoid second operation for its remove, and enable to promote bone repair; however, the underlying molecular mechanisms remain unclear. In the present study, we examined the effect of Mg ions on osteogenesis, chemotaxis and anti-alkaline stress in hFOB1.19 human osteoblast cells to simulate bone-repairing effect of a biodegradable Mg-based alloy implant in vitro, and explored the regulatory role of the transient receptor potential melastatin 7 (TRPM7)/phosphoinositide 3-kinase (PI3K) signalling pathway in the process of Mg ion-induced bone repair by knockdown of TRPM7 and antagonizing PI3K activity. Results indicate that Mg ions up-regulated the expression of Runx2 and alkaline phosphatase (ALP) through TRPM7/PI3K signalling pathway, which could significantly enhance the osteogenic activity of human osteoblasts. Furthermore, the expression levels of MMP2, MMP9 and vascular endothelial growth factor (VEGF) were increased by TRPM7/PI3K signalling pathway, which recruits osteoblasts from low- to high-Mg ion environments by inducing cell migration. Although an alkaline environment has antibacterial effects, alkaline stress can cause cytotoxicity and induce cell death. Finally, we found that Mg ions could activate PI3K phosphorylation to promote cell growth and survival, protecting cells against the alkaline-stress-induced cytotoxicity caused by the degradation of Mg-based alloy implants. Our study not only revealed the molecular mechanism of Mg in promoting bone repair but also explained the protective effects of Mg ions on osteoblasts in an alkaline environment, which provides a theoretical basis and new directions for the application of Mg-based alloy implant material in orthopaedics fixations and osteosarcoma treatment. STATEMENTS OF SIGNIFICANCE As a potential biomaterial for orthopaedic implant, biodegradable magnesium has several advantages including self-degradation and bone repair promotion; however, the underlying mechanisms and effective concentration by which molecular regulates the bone repair remain unclear. The present study revealed that Mg ion and its effective concentration for activating PI3K phosphorylation via TRPM7, which causes three processes affecting bone repair, namely, osteoblast recruitment, osteogenesis and resistance to alkaline stress in human osteoblast. Therefore, our results have provided insight into the underlying molecular biological basis, and guidance for manipulating degradation rate, such as surface modification, of orthopaedic Mg-based implants.

Revascularization of the femoral head by anastomosis of superior retinacular vessels for the treatment of femoral neck fracture: A case report.

The purpose of this report is to present a method of revascularization of the femoral head for the treatment of femoral neck fracture in a young adult. The patient is a 22‐year‐old male with the femoral neck fracture of Garden type III. We performed an open reduction with internal fixation of the fracture and repaired the superior retinacular vessels using microsurgical techniques to achieve revascularization to the femoral head. A desensitized‐digital subtraction angiography examination showed that the blood supply from the superior retinacular artery to the femoral head was re‐established three months after surgery. The X‐ray showed that the femoral head had a normal shape without any necrotic lesions or sclerotic changes at four months follow‐up and the bone achieved good union without redisplacement of the fracture site. This case showed that revascularization of the femoral head by microsurgery could be feasible in treatment of certain type of femoral neck fracture.

Micro Perfusion and Quantitative Analysis of the Femoral Head Intraosseous Artery: Artery Micro Perfusion And Quantification

The present study investigates the feasibility of micro perfusion of femoral head specimens from femoral neck fracture patients by the inferior retinacular arteries and performing intraosseous artery quantitative analysis of the femoral head. Twelve femoral neck fracture patients who had undergone conventional hip replacement surgery were included in this study. Femoral head specimen arteries were first dissected and exposed and then perfused by the inferior retinacular arteries and all the femoral heads underwent micro‐CT scanning. After micro‐CT scanning, a digital 3‐D model was reconstructed to quantify the femoral head intraosseous arteries for comparison with a normal femoral head. The artery length density, artery volume density, and artery length/volume ratio were calculated separately and compared with normal femoral head parameters. Micro‐CT scanning displayed the epiphyseal arterial network structure and their fine vascular branches in all 12 femoral neck fractures. Blood was supplied from the inferior retinacular artery to the epiphyseal arterial network then to all the fine blood vessels within the femoral head. No statistical differences were observed in femoral heads’ intraosseous artery length densities or volume densities between the normal and femoral neck fracture specimens, while the artery length/volume ratio showed a statistical difference, and the ratio increased from 19 to 46. Micro perfusion of the femoral head by the inferior retinacular arteries is possible and can present the epiphyseal network and their fine arterial branches in pathologic conditions to provide a morphological basis for the study of femoral head disease.

Safflower (Carthamus tinctorius L.) polysaccharide attenuates cellular apoptosis in steroid-induced avascular necrosis of femoral head by targeting caspase-3-dependent signaling pathway

The present study aimed to investigate the effects of a purified polysaccharide (SPS) from the safflower in a cellular model of steroid-associated necrosis of the femoral head (SANFH), which was established in primary murine osteoblasts suffering dexamethasone pretreatment. After treatment with SPS (25, 50 and 100 μg/ml), the degree of necrosis induced by dexamethasone was significantly reduced in osteoblasts as evidenced by an increase of cell viability and a decrease of apoptosis in osteoblasts. Furthermore, pretreatment with SPS (25, 50 and 100 μg/ml) significantly attenuated the activation of caspase-3 and cleavage of PARP relative to the model control cells. The addition of caspase-3 inhibitor (Z-DEVD-FMK) in dexamethasone-treated osteoblasts resulted in the inefficiency of SPS for inhibiting cellular apoptosis. Dose-dependent increases in alkaline phosphatase (ALP) activity, collagen synthesis and mineralization were also observed in SPS-treated osteoblasts at 72 h. The present study demonstrates that SPS may alleviate dexamethasone associated osteonecrosis by inhibiting caspsae-3-mediated apoptosis and may provide an alternative treatment for SANFH.