Subchondral Bone Reconstruction Research Articles

Bergenin protects against osteoarthritis by inhibiting STAT3, NF-κB and Jun pathways and suppressing osteoclastogenesis

Osteoarthritis (OA) is a chronic degenerative disease characterized by articular cartilage destruction and subchondral bone reconstruction in the early stages. Bergenin (Ber) is a cytoprotective polyphenol found in many medicinal plants. It has been proven to have anti-inflammatory, antioxidant, and other biological activities, which may reveal its potential role in the treatment of OA. This study aimed to determine the potential efficacy of Ber in treating OA and explore the possible underlying mechanism through network pharmacology and validation experiments. The potential co-targets and processes of Ber and OA were predicted by using network pharmacology, including a Venn diagram for intersection targets, a protein‒protein interaction (PPI) network to obtain key potential targets, and GO and KEGG pathway enrichment to reveal the probable mechanism of action of Ber on OA. Subsequently, validation experiments were carried out to investigate the effects and mechanisms of Ber in treating OA in vitro and vivo. Ber suppressed IL-1β-induced chondrocyte apoptosis and extracellular matrix catabolism by inhibiting the STAT3, NF-κB and Jun signalling pathway in vitro. Furthermore, Ber suppressed the expression of osteoclast marker genes and RANKL-induced osteoclastogenesis. Ber alleviated the progression of OA in DMM-induced OA mice model. These results demonstrated the protective efficacy and potential mechanisms of Ber against OA, which suggested that Ber could be adopted as a potential therapeutic agent for treating OA.

A Hybrid Scaffold Induces Chondrogenic Differentiation and Enhances In Vivo Cartilage Regeneration.

Extensively researched tissue engineering strategies involve incorporating cells into suitable biomaterials, offering promising alternatives to boost tissue repair. In this study, a hybrid scaffold, Gel-DCM, which integrates a photoreactive gelatin-hyaluronic acid hydrogel (Gel) with an oriented porous decellularized cartilage matrix (DCM), was designed to facilitate chondrogenic differentiation and cartilage repair. The Gel-DCM exhibited excellent biocompatibility in vitro, promoting favorable survival and growth of human adipose-derived stem cells (hADSCs) and articular chondrocytes (hACs). Gene expression analysis indicated that the hACs expanded within the Gel-DCM exhibited enhanced chondrogenic phenotype. In addition, Gel-DCM promoted chondrogenesis of hADSCs without the supplementation of exogenous growth factors. Following this, invivo experiments were conducted where empty Gel-DCM or Gel-DCM loaded with hACs/hADSCs were used and implanted to repair osteochondral defects in a rat model. In the control group, no implants were delivered to the injury site. Interestingly, macroscopic, histological, and microcomputed tomography scanning results revealed superior cartilage restoration and subchondral bone reconstruction in the empty Gel-DCM group compared with the control group. Moreover, both hACs-loaded and hADSCs-loaded Gel-DCM implants exhibited superior repair of hyaline cartilage and successful reconstruction of subchondral bone, whereas defects in the control groups were predominantly filled with fibrous tissue. These observations suggest that the Gel-DCM can provide an appropriate three-dimensional chondrogenic microenvironment, and its combination with reparative cell sources, ACs or ADSCs, holds great potential for facilitating cartilage regeneration.

Paroxetine Attenuates Chondrocyte Pyroptosis and Inhibits Osteoclast Formation by Inhibiting NF-κB Pathway Activation to Delay Osteoarthritis Progression.

Osteoarthritis (OA), a common chronic joint disease, is characterized by cartilage degeneration and subchondral bone reconstruction. NF-κB signaling pathway-activated inflammation and NLRP3-induced pyroptosis play essential roles in the development of OA. In this study, we examine whether paroxetine can inhibit pyroptosis and reduce osteoclast formation, thereby delaying the destruction of knee joints. We employed high-density cultures, along with quantitative polymerase chain reactions and Western blotting techniques, to investigate the effects of paroxetine on extracellular matrix synthesis and degradation. The expression levels of NF-κB and pyroptosis-related signaling pathway proteins were examined by Western blotting and immunofluorescence. Furthermore, the impact of paroxetine on RANKL-induced osteoclast formation was evaluated through TRAP staining and F-actin ring fluorescence detection. To investigate the role of paroxetine in vivo, we constructed a mouse model with destabilization of the medial meniscus (DMM) surgery. Safranin O-Fast Green staining, Hematoxylin-Eosin staining, and immunohistochemistry were conducted to observe the extent of knee joint cartilage deformation. In addition, TRAP staining was used to observe the formation of osteoclasts in the subchondral bone. In the in vitro experiments with ATDC5, paroxetine treatment attenuated IL-1β-induced activation of the pyroptosis-related pathway and suppressed extracellular matrix catabolism by inhibiting the NF-kB signaling pathway. In addition, paroxetine treatment decreased the expression of RANKL-induced osteoclast marker genes and reduced osteoclast formation. In animal experiments conducted in vivo, mice treated with paroxetine exhibited thicker knee cartilage with a smoother surface compared to the DMM group. Additionally, the formation of osteoclasts in the subchondral bone was reduced in the paroxetine-treated mice. Further analysis revealed that paroxetine treatment played a role in preserving the balance of the extracellular matrix and delaying knee joint degeneration. Paroxetine can inhibit pyroptosis and reduce osteoclast formation via inhibiting the NF-κB signaling pathway, suggesting that it may have therapeutic effects in patients with OA.

Research progress on etiology and establishment of mouse model of knee osteoarthritis

Knee osteoarthritis is the most common degenerative joint disease in the elderly. Knee osteoarthritis is mainly due to the degeneration and loss of articular cartilage, subchondral bone reconstruction and periarticular osteophyte formation and other factors, resulting in joint pain, limited movement and ultimately joint dysfunction. Knee osteoarthritis is caused by multiple factors, and with the aging of the population and obesity epidemic, the number of symptomatic knee osteoarthritis patients will increase significantly. Due to the complexity and diversity of its etiology, there is a lack of effective treatment to improve or delay the progression of knee osteoarthritis. For those patients with severe pain or joint injury, only surgical treatment (unicompartmental knee arthroplasty or total knee arthroplasty) brings heavy burden to the economy and society. Therefore, there is an urgent need to build an ideal animal model and make an in-depth study on the pathophysiological mechanism of different etiology of the disease. Because mammals have a knee joint anatomical structure like that of human beings, and there are many loads on the lower limbs, therefore, the current researchers mainly use mammalian mice (small size, low price, strong viability, low requirements for feeding conditions, etc.) to prepare corresponding animal models for research. In this paper, through the systematic literature and summary of previous studies, the rat model of knee osteoarthritis was analyzed and summarized according to heredity, spontaneity, obesity and surgical induction through etiological classification. to provide some theoretical basis and support for follow-up experimental research.

Eucommia ulmoides Polysaccharides Attenuate Rabbit Osteoarthritis by Regulating the Function of Macrophages.

Background and purpose:Eucommia ulmoides polysaccharides (EUP) can regulate the immunity of macrophages, but the functional status of macrophages is related to osteoarthritis and synovial inflammation. The purpose of this study is to explore whether EUP has the effect of inhibiting osteoarthritis and its possible mechanism.Methods: MTT test was used to evaluate the appropriate concentration of EUP and real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to detect the effect of EUP on gene expression in RAW 264.7 cells. The osteoarthritis model was constructed by the anterior cruciate ligament transection (ACLT) in the rabbits. These rabbits were divided into three groups, sham operation group, OA group, and EUP group. The changes in articular cartilage were detected by gross observation and histological staining, and Micro-CT tested subchondral bone. Finally, the changes of macrophages in synovial tissue were studied by immunohistochemistry.Results: The results showed that EUP at the concentration of 50ug/mL and 100ug/mL were beneficial to the proliferation of macrophages. The qPCR results indicated that EUP inhibited the expression of inflammation-related genes IL-6, IL-18 and IL-1β, and promoted the expression of osteogenic and cartilage-related genes BMP-6, Arg-1 and transforming growth factor beta (TGF-β). The results of in vivo experiments suggested that the degree of destruction of articular cartilage in the EUP group was significantly reduced, and the Osteoarthritis Research Society International (OARSI) score was significantly reduced. Compared with the OA group, the subchondral cancellous bone density of the EUP group increased, the number and thickness of trabecular bone increased, and the separation of trabecular bone decreased. Synovial macrophage immunohistochemistry results manifested that EUP, on the one hand, reduced M1 polarized macrophages, on the other hand, accumulated M2 polarized macrophages.Conclusion: EUP can promote articular cartilage repair and subchondral bone reconstruction. The regulation of the polarization state of macrophages may be one of its mechanisms to delay the progression of osteoarthritis.

Three-dimensional-printed porous implant combined with autograft reconstruction for giant cell tumor in proximal tibia

BackgroundThis study is to describe the design and surgical techniques of three- dimensional-printed porous implants for proximal giant cell tumors of bone and evaluate the short-term clinical outcomes.MethodsFrom December 2016 to April 2020, 8 patients with giant cell tumor of bone in the proximal tibia underwent intralesional curettage of the tumor and reconstruction with bone grafting and three-dimensional-printed porous implant. Detailed anatomy data were measured, including the size of lesion and thickness of the subchondral bone. Prostheses were custom-made for each patient by our team. All patients were evaluated regularly and short-term clinical outcomes were recorded.ResultsThe mean follow-up period was 26 months. According to the different defect sizes, the mean size of the plate and mean length of strut were 35 × 35 mm and 20 mm, respectively. The mean affected subchondral bone percentage was 31.5%. The average preoperative and postoperative thickness of the subchondral bone was 2.1 mm and 11.1 mm, respectively. There was no wound infection, skin necrosis, peroneal nerve injury, or other surgical related complications. No degeneration of the knee joint was found. Osseointegration was observed in all patients. The MSTS improved from an average of 12 preoperatively to 28 postoperatively.ConclusionThe application of three-dimensional-printed printed porous prosthesis combined autograft could supply enough mechanical support and enhance bone ingrowth. The design and operation management lead to satisfactory subchondral bone reconstruction.

Extracellular matrix derived from allogenic decellularized bone marrow mesenchymal stem cell sheets for the reconstruction of osteochondral defects in rabbits

Bioactive scaffolds from synthetical polymers or decellularized cartilage matrices have been widely used in osteochondral regeneration. However, the risks of potential immunological reactions and the inevitable donor morbidity of these scaffolds have limited their practical applications. To address these issues, a biological extracellular matrix (ECM) scaffold derived from allogenic decellularized bone marrow mesenchymal stem cell (BMSC) sheets was established for osteochondral reconstruction. BMSCs were induced to form cell sheets. Three different concentrations of sodium dodecyl sulfate (SDS), namely, 0.5%, 1%, and 3%, were used to decellularize these BMSC sheets to prepare the ECM. Histological and microstructural observations were performed in vitro and then the ECM scaffolds were implanted into osteochondral defects in rabbits to evaluate the repair effect in vivo. Treatment with 0.5% SDS not only efficiently removed BMSCs but also successfully preserved the original structure and bioactive components of the ECM When compared with the 1% and 3% SDS groups, histological observations substantiated the superior repair effect of osteochondral defects, including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular cartilage integrated with native tissues in the 0.5% SDS group. Moreover, RT-PCR indicated that ECM scaffolds could promote the osteogenic differentiation potential of BMSCs under osteogenic conditions while increasing the chondrogenic differentiation potential of BMSCs under chondrogenic conditions. Allogenic BMSC sheets decellularized with 0.5% SDS treatment increased the recruitment of BMSCs and significantly improved the regeneration of osteochondral defects in rabbits, thus providing a prospective approach for both articular cartilage and subchondral bone reconstruction with cell-free transplantation.

An Injectable Hydrogel Scaffold With Kartogenin-Encapsulated Nanoparticles for Porcine Cartilage Regeneration: A 12-Month Follow-up Study

Background: Treatment of cartilage lesions is clinically challenging. A previous study demonstrated that a hyaluronic acid hydrogel (m-HA) with kartogenin (KGN)-loaded PLGA nanoparticles (m-HA+KGN treatment) achieved superior cartilage repair in a rabbit model. However, large animals serve as a bridge to translate animal outcomes into the clinic. Hypotheses: (1) m-HA+KGN treatment could facilitate hyaline cartilage and subchondral bone tissue repair in a porcine model. (2) Defect size and type (full-thickness chondral vs osteochondral) influence the therapeutic efficacy of m-HA+KGN treatment. Study Design: Controlled laboratory study. Methods: 48 minipigs were randomized into 3 treatment groups: m-HA hydrogel with KGN-loaded PLGA nanoparticles (m-HA+KGN treatment), m-HA hydrogel (m-HA treatment), and untreated (blank treatment). Full-thickness chondral (6.5 mm or 8.5 mm in diameter) or osteochondral (6.5 mm or 8.5 mm in diameter; 5-mm depth) defects were prepared in the medial femoral condyle. At 6 and 12 months postoperatively, defect repair was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (µCT), and histologic and biomechanical tests. Results: The m-HA+KGN group exhibited superior gross and histological healing after evaluation at 6 and 12 months postoperatively. Improved quality of the repaired cartilage demonstrated by MRI and better subchondral bone reconstruction assessed by µCT were observed in the m-HA+KGN group. The m-HA+KGN group showed more hyaline-like cartilage exhibited by histological staining in terms of extracellular matrix, cartilage lacuna, and type II collagen. The biomechanical properties were improved in the m-HA+KGN group. With m-HA+KGN treatment, defects with a diameter of 6.5 mm or full-thickness chondral-type defects possessed significantly higher ICRS macroscopic and histological scores compared with diameter 8.5 mm or osteochondral-type defects. Conclusion: (1) m-HA+KGN treatment facilitated hyaline cartilage and subchondral bone tissue repair in a porcine model at the 12-month follow-up. (2) m-HA+KGN treatment demonstrated better therapeutic efficacy in defects with a diameter of 6.5 mm or full-thickness chondral-type defects. Clinical Relevance: This study verified the efficacy of this innovative KGN release system on cartilage repair. The KGN release system can be injected into defect sites arthroscopically. This convenient and minimally invasive operation holds important prospects for clinical application.

Comparison of early-stage changes of osteoarthritis in cartilage and subchondral bone between two different rat models.

Osteoarthritis (OA) is a chronic degenerative joint disease and the major cause of joint pain and disability in the elderly. It is mainly characterized by articular cartilage degradation and subchondral bone remodeling. There are two main types of OA: natural occurring OA and secondary OA, mainly associated with aging and trauma, respectively. In this study, we established two OA models in rat knee joints to simulate the two types of OA, using the type II collagenase injection (CI) and anterior cruciate ligament transection (ACLT), respectively. After intervention for 2–6 weeks, cartilage and subchondral bone changes were detected in histological staining, immunochemistry, and micro-CT. Results showed that both models with typical pathology changes of OA were successfully induced, while the development and severity of OA process in the models were different. In ACLT rats, the cartilage damage was milder, lasted for a shorter time, and subchondral bone reconstruction occurred earlier, compared with the changes in CI rats. The cartilage damage was secondary to subchondral bone change in ACLT rats, while subchondral bone change was secondary to cartilage degeneration in CI rats. In conclusion, the interaction between cartilage and subchondral bone is different between the natural-occurring and secondary OA models. These two models not only suggest potential different mechanisms of the two types of OA, but also provide new directions for OA treatment and prevention.

Autologous Micro-Fragmented Adipose Tissue as Stem Cell-Based Natural Scaffold for Cartilage Defect Repair

Osteoarthritis (OA) poses a tough challenge worldwide. Adipose-derived stem cells (ASCs) have been proved to play a promising role in cartilage repair. However, enzymatic digestion, ex vivo culture and expansion, with significant senescence and decline in multipotency, limit their application. The present study was designed to obtain micro-fragmented adipose tissue (MFAT) through gentle mechanical force and determine the effect of this stem cell-based natural scaffold on repair of full-thickness cartilage defects. In this study, ASCs sprouted from MFAT were characterized by multi-differentiation induction and flow cytometry. Scratch and transwell migration assays were operated to determine whether MFAT could promote migration of chondrocytes in vitro. In a rat model, cartilage defects were created on the femoral groove and treated with intra-articular injection of MFAT or PBS for 6 weeks and 12 weeks (n = 12). At the time points, the degree of cartilage repair was evaluated by histological staining, immunohistochemistry and scoring, respectively. Two unoperated age-matched animals served as native controls. ASCs derived from MFAT possessed properties to differentiate into adipocytes, osteocytes and chondrocytes, with expression of mesenchymal stem cell markers (CD29, 44, 90) and no expression of hematopoietic markers (CD31, 34, 45). In addition, MFAT could significantly promote migration of chondrocytes. MFAT-treated defects showed improved macroscopic appearance and histological evaluation compared with PBS-treated defects at both time points. After 12 weeks of treatment, MFAT-treated defects displayed regular surface, high amount of hyaline cartilage, intact subchondral bone reconstruction and corresponding formation of type I, II, and VI collagen, which resembled the normal cartilage. This study demonstrates the efficacy of MFAT on cartilage repair in an animal model for the first time, and the utility of MFAT as a ready-to-use therapeutic alternative to traditional stem cell therapy.

An exploratory study of articular cartilage and subchondral bone reconstruction with bone marrow mesenchymal stem cells combined with porous tantalum/Bio-Gide collagen membrane in osteonecrosis of the femoral head

Osteonecrosis of the femoral head (ONFH) results in collapse of the femoral head and rapid destruction of the hip joint. The repair of post-collapse articular cartilage and subchondral bone is challenging. We interrupted the blood supply to the femoral head and established a full-thickness articular defect animal model after ONFH was determined via X-ray. Porous tantalum and a Bio-Gide collagen membrane, co-cultured with bone marrow mesenchymal stem cells (BMSCs) in vitro, were implanted into the defect zone to repair the full-thickness articular defect. Hyaline cartilage was detected on top of the tantalum near the edge of the defect 12 weeks post-operatively. Porous tantalum and a Bio-Gide collagen membrane with BMSCs may repair full-thickness articular defects if the blood supply can be reconstructed in the post-collapse stage of ONFH.

Tougu Xiaotong capsule exerts a therapeutic effect on knee osteoarthritis by regulating subchondral bone remodeling.

Previous studies have shown that Tougu Xiaotong capsule (TGXTC) has therapeutic effects on knee osteoarthritis(OA) through multiple targets. However, the mechanisms of action underlying its regulation of subchondral bone reconstruction remain unclear. In this study, we investigated the effects of TGXTC on subchondral bone remodeling. Eighteen six-month-old New Zealand white rabbits of average sex were randomly divided into the normal, model and TGXTC groups. The rabbit knee OA model was induced by a modified Hulth's method in the model and TGXTC groups, but not the normal group. Five weeks postoperatively, intragastric administration of TGXTC was performed for four weeks. After drug administration, the medial femoral condyle and tibia were prepared for observation of cartilage histology via optical microscopy and micro-computed tomography, the serum was collected for biochemical parameters assay and the subchondral bone isolated from the lateral femoral condyle was collected for detection of IL-1β and TNF-α mRNA and protein by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The results showed that treatment with TGXTC significantly mitigated cartilage injury and subchondral bone damage, improved the parameter of subchondral trabecular bone, decreased alkaline phosphatase and tartrate-resistant acid phosphatase activity, and significantly reducing the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio, reduced the expression of IL-1β and TNF-α mRNA and protein. These results suggest that TGXTC could delay the pathological development of OA by regulating subchondral bone remodeling through regulation of bone formation and bone resorption and its relating inflammatory factors, and this may partly explain its clinical efficacy in the treatment of knee OA.

In Situ Articular Cartilage Regeneration through Endogenous Reparative Cell Homing Using a Functional Bone Marrow-Specific Scaffolding System.

In situ tissue regeneration by homing endogenous reparative cells to the injury site has been extensively researched as a promising alternative strategy to facilitate tissue repair. In this study, a promising scaffolding system DCM-RAD/SKP, which integrated a decellularized cartilage matrix (DCM)-derived scaffold with a functionalized self-assembly Ac-(RADA)4-CONH2/Ac-(RADA)4GGSKPPGTSS-CONH2 (RAD/SKP) peptide nanofiber hydrogel, was designed for repairing rabbit osteochondral defect. In vitro experiments showed that rabbit bone marrow stem cells migrated into and have higher affinity toward the functional scaffolding system DCM-RAD/SKP than the control scaffolds. One week after in vivo implantation, the functional scaffolding system DCM-RAD/SKP facilitated the recruitment of endogenous mesenchymal stem cells within the defect site. Moreover, gene expression analysis indicated that the DCM-RAD/SKP promoted chondrogenesis of the recruited cells. In vivo results showed that the DCM-RAD/SKP achieved superior hyaline-like cartilage repair and successful subchondral bone reconstruction. By contrast, the control groups mostly led to fibrous tissue repair. These findings indicate that the DCM-RAD/SKP can recruit endogenous stem cells into the site of cartilage injury and promote differentiation of the infiltrating cells into the chondrogenic lineage, holding great potential as a one-step surgery strategy for cartilage repair.

Layered gelatin/PLLA scaffolds fabricated by electrospinning and 3D printing- for nasal cartilages and subchondral bone reconstruction

In the present work the advantages of two kinds of different, well known and applicable, biomaterials (PLLA and gelatin) and two kinds of scaffold fabrication techniques (3D printing - FDM and electrospinning) were combined in order to create a novel multifunctional layered scaffold for nasal cartilages and subchondral bone reconstruction. The pore size of scaffolds produced by 3D printing technology was designed to solve the problem that otolaryngologists currently have with fixing the nasal cartilage implant with needle and threads. The effect of the solution concentration for the electrospinning process on the microstructure and mechanical properties of gelatin nanofibers produced as well as the influence of drug concentration on the mechanical properties of membranes were investigated. The commercially available FDM – 3D printing system was used. 3D scaffolds varying in structure and geometry were designed and printed. The influence of the internal architecture of 3D printed scaffolds on their mechanical properties was tested. Hybrid layered scaffolds consisting of a top gelatin nanofibrous layer and a bottom 3D printed porous PLLA material were developed. The mineralization ability of a scaffold was determined in simulated body fluid. The cytotoxicity, proliferation and morphology of Murine fibroblasts L929 cultured on obtained biomaterials were evaluated.

Bioactive Scaffolds for Regeneration of Cartilage and Subchondral Bone Interface.

The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr5(PO4)2SiO4 (SPS) bioactive ceramic scaffolds may achieve the aim of regenerating both of cartilage and subchondral bone. We hypothesized that strontium (Sr) and silicon (Si) ions released from SPS scaffolds play a crucial role in osteochondral defect reconstruction.Methods: SPS bioactive ceramic scaffolds were fabricated by a 3D-printing method. The SEM and ICPAES were used to investigate the physicochemical properties of SPS scaffolds. The proliferation and maturation of rabbit chondrocytes stimulated by SPS bioactive ceramics were measured in vitro. The stimulatory effect of SPS scaffolds for cartilage and subchondral bone regeneration was investigated in vivo.Results: SPS scaffolds significantly stimulated chondrocyte proliferation, and SPS extracts distinctly enhanced the maturation of chondrocytes and preserved chondrocytes from OA. SPS scaffolds markedly promoted the regeneration of osteochondral defects. The complex interface microstructure between cartilage and subchondral bone was obviously reconstructed. The underlying mechanism may be related to Sr and Si ions stimulating cartilage regeneration by activating HIF pathway and promoting subchondral bone reconstruction through activating Wnt pathway, as well as preserving chondrocytes from OA via inducing autophagy and inhibiting hedgehog pathway.Conclusion: Our findings suggest that SPS scaffolds can help osteochondral defect reconstruction and well reconstruct the complex interface between cartilage and subchondral bone, which represents a promising strategy for osteochondral defect regeneration.

The effects of different doses of IGF-1 on cartilage and subchondral bone during the repair of full-thickness articular cartilage defects in rabbits

To investigate the effects of different doses of insulin-like growth factor 1 (IGF-1) on the cartilage layer and subchondral bone (SB) during repair of full-thickness articular cartilage (AC) defects. IGF-1-loaded collagen membrane was implanted into full-thickness AC defects in rabbits. The effects of two different doses of IGF-1 on cartilage layer and SB adjacent to the defect, the cartilage structure, formation and integration, and the new SB formation were evaluated at the 1st, 4th and 8th week postoperation. Meanwhile, after 1 week treatment, the relative mRNA expressions in tissues adjacent to the defect, including cartilage and SB were determined by quantitative real-time RT-PCR (qRT-PCR), respectively. Different doses of IGF-1 induced different gene expression profiles in tissues adjacent to the defect and resulted in different repair outcomes. Particularly, at high dose IGF-1 aided cell survival, regulated the gene expressions in cartilage layer adjacent defect and altered ECM composition more effectively, improved the formation and integrity of neo-cartilage. While, at low dose IGF-1 regulated the gene expressions in SB more efficaciously and subsequently promoted the SB remodeling and reconstruction. Different doses of IGF-1 induced different responses of cartilage or SB during the repair of full-thickness AC defects. Particularly, high dose of IGF-1 was more beneficial to the neo-cartilage formation and integration, while low dose of it was more effective for the SB formation.

Inhibition of Osteoarthritis in Rats by Electroporation with Interleukin-1 Receptor Antagonist

Gene therapy constitutes a promising strategy for the treatment of osteoarthritis (OA). We assessed the use of electroporation (EP) of non-viral gene vectors, and compared its efficacy with that of adeno-associated virus (AAV) vectors. EP- and AAV-mediated delivery of human interleukin-1 receptor antagonist (hIL-1Ra) was localized performed in the joints of rats following induction of OA. mRNA levels for hIL-1Ra, IL-1β, TNF-α, MMP-13 and ADAMTS-4 in the cartilage and synovial tissues were analyzed. Structural analyses of the subchondral bone at the medial femoral condyle were performed by Micro-CT after treatment. Knee joint specimens were staining with hematoxylin and eosin and Saffron O. Induction of hIL-1Ra by both EP and AAV inhibited inflammatory-induced sub-chondral bone reconstruction, and effectively suppressed IL-1β activity, as evidenced by decreased expression of MMP-13 and ADAMTS-4. Histological analyses revealed significant protection of cartilage, proteoglycan by EP and AAV. hIL-1Ra expression was similar in both the EP and AAV groups. Notably, this gene is not easier degraded transduced by EP compared with AAV. Taken together, these results show that EP offers transfection efficiency comparable to that of AAV, with the potential for longer gene expression, making EP a promising candidate for efficient non-viral delivery of OA gene therapy.

Repair of articular cartilage defects with a novel injectablein situforming material in a canine model

We developed an ultra-purified in situ forming gel as an injectable delivery vehicle of bone marrow stromal cells (BMSCs). Our objective was to assess reparative tissues treated with autologous BMSCs implanted using the injectable implantation system into osteochondral defects in a canine model. Forty-eight osteochondral defects in the patella groove of the knee joint were created in 12 adult beagle dogs (two defects in each knee). The defects were divided into a defect group (n = 16), an acellular novel material implantation (material) group (n = 16), and a BMSCs implantation using the current vehicle system (material with BMSCs) group (n = 16). The reparative tissues at 16 weeks postoperatively were assessed through gross, histological, and mechanical analyses. The reparative tissues of the material with BMSCs group were substituted with firm and smooth hyaline-like cartilage tissue that was perfectly integrated into the host tissues. This treatment group obviously enhanced the subchondral bone reconstruction. The compressive modulus of the reparative tissues was significantly higher in the material with BMSCs group than the other groups. This study demonstrated that the implantation of BMSCs using our novel in situ forming material induced a mature hyaline-like cartilage repair of osteochondral defects in a canine model.

A case report: Reconstruction of a damaged knee following treatment of giant cell tumor of the proximal tibia with cryosurgery and cementation

Objective Reconstruction of a knee damaged by cement packed to cure a giant-cell tumor is sometimes difficult. We reconstructed such a knee by removal of the cement, autologous bone transplantation and distraction osteogenesis using the Ilizarov apparatus. In this paper the results 29 months after the salvage surgery are given.Patient and Methods We saw a 31-year-old woman's knee joint that showed osteoarthritic change after curettage, cryosurgery and cementation performed 4 years previously for a giant-cell tumor of the proximal tibia. We reconstructed the knee joint. This procedure included cement removal, alignment correction by tibial osteotomy, subchondral bone reconstruction by autologous bone transplantation, and filling the defect after removing the bone cement by elongating the diaphysis using the Ilizarov apparatus.Results Distraction was terminated 4 months later when 54mm of elongation was performed. All devices were removed 12 months after the surgery. Seventeen months after the removal of the apparatus, the range of motion of the right knee was 0° extension and 110° flexion, and the patient was able to walk without pain.Conclusions Although the treatment period is long and there may be some complications of Ilizarov lengthening and distraction osteogenesis, this procedure has numerous benefits. Bony defects can be soundly reconstructed and, at the same time, the alignment of the knee can be corrected. Also it is not necessary to reconstruct the ligaments because the insertions are intact. If osteoarthritis progresses, a surface type total knee replacement can be performed, not constrained type prosthesis, which would be used if the bony structure had not been reconstructed. This procedure may be one of the candidates for reconstructing such knee joints destroyed by bone cement. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.