No Difference in Bone Tunnel Enlargement and Clinical Outcome between Cortical Suspension and Hybrid Femoral Fixation in Hamstring Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: The best method for femoral fixation in anterior cruciate ligament reconstruction (ACLR) remains controversial. The study assesses the bone tunnel enlargement and clinical outcome in hamstring ACLR using cortical suspension or hybrid (cortical suspension and compression) femoral fixation. METHODS: From January 2010 to December 2021, 102 patients who underwent quadruple hamstring ACLR using cortical suspension (39 patients) or hybrid (63 patients) fixation on the femoral side were retrospectively analyzed. Clinical evaluation was conducted using the international knee documentation committee score, the Lysholm score, the Tegner activity level scale, the knee injury and osteoarthritis outcome score (quality of life score), the Lachman test, and the side-to-side difference by the KT-1000 arthrometer. The complications after the surgery were also evaluated. These data were compared at baseline and last follow-up. The diameters of the femoral tunnel were calculated at three sites: the width of the entrance of the femoral tunnel, 1 cm proximal to the entrance of the femoral tunnel and the largest diameter of the femoral tunnel on magnetic resonance imaging (MRI) coronal images. Bone tunnel widening data were contrasted between MRI images conducted at least 2 years and within 2 weeks after surgery. The morphology of bone tunnel enlargement was also observed and recorded. The categorical parameters were analyzed using the χ2-test and Fisher's exact test. The continuous variables conforming to a normal distribution were analyzed using Student's t-test, and the Mann-Whitney U-test was undertaken between the two groups without normal distribution. RESULTS: Both cortical suspension and hybrid femoral fixation in quadruple hamstring ACLR achieved significantly improved patient-reported outcome scores and knee stability compared to preoperative data. However, no significant differences were found between these two methods in clinical evaluations, postoperative complications, and patient-reported outcome scores. Although the mean diameter of the enlarged bone tunnel was lowered by an additional bioabsorbable interference screw fixation near the joint line, a statistically insignificant difference was found between the hybrid and cortical suspension fixation on the femoral side. There was no statistical difference in the distribution of enlarged bone tunnel morphology between groups. CONCLUSIONS: No significant difference was found in the bone tunnel enlargement and clinical outcome between cortical suspension and hybrid femoral fixation in ACLR using hamstring autograft.

Adipose-derived mesenchymal stromal cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis.

Osteoclasts are responsible for bone destruction in rheumatoid arthritis (RA), and adipose-derived mesenchymal stromal cells (ADSCs) can inhibit experimental collagen-induced arthritis model. This study aims to determine whether ADSCs also suppresses osteoclastogenesis and bone erosion in collagen-induced arthritis (CIA). Osteoclasts were induced from bone marrow-derived CD11b+ cells with receptor activator of nuclear factor-κ B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) stimulation and assessed with tartrate-resistant acid phosphatase (TRAP) staining. For human cells, osteoclasts were produced from human CD14+ cells. ADSCs were generated and added to cultures with different ratios with CD11b+ cells. Transwell and antibody blockade experiments were performed to define the mechanism of action. NF-κB and RANKL expression were determined by Western blotting and RT-qPCR. About 2 × 106 ADSCs or fibroblast cells were adoptively transferred to DBA1/J mice on day 14 after immunization with type II collagen/complete Freund's adjuvant (CII/CFA) while the onset and severity of the CIA were monitored. Adipose-derived mesenchymal stromal cells but not fibroblast cells completely suppressed osteoclastogenesis in vitro for human and mice. ADSCs injected after immunization and before of onset of CIA significantly suppressed disease development. Treatment with ADSCs dramatically decreased the levels of NF-κB p65/p50 in osteoclasts in vitro and P65/50 and RANKL expression by synovial tissues in vivo. We have demonstrated that ADSCs can inhibit RANKL-induced osteoclasts genesis via CD39 signals. Our findings also suggest that ADSCs can inhibit osteoclasts genesis without the involvement of regulatory T cells. ADSCs might represent a promising strategy for stem cell-based therapies for RA. Thus, manipulation of ADSCs may have therapeutic effects on RA and other bone erosion-related diseases.

Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation.

Notochord nucleus pulposus cells are characteristic of containing abundant and giant cytoplasmic vacuoles. This review explores the embryonic formation, biological function, and postnatal exhaustion of notochord vacuoles, aiming to characterize the signal network transforming the vacuolated nucleus pulposus cells into the vacuole-less chondrocytic cells. Embryonically, the cytoplasmic vacuoles within vertebrate notochord originate from an evolutionarily conserved vacuolation process during neurulation, which may continue to provide mechanical and signal support in constructing a mammalian intervertebral disc. For full vacuolation, a vacuolating specification from dorsal organizer cells, synchronized convergent extension, well-structured notochord sheath, and sufficient post-Golgi trafficking in notochord cells are required. Postnatally, age-related and species-specific exhaustion of vacuolated nucleus pulposus cells could be potentiated by Fas- and Fas ligand-induced apoptosis, intolerance to mechanical stress and nutrient deficiency, vacuole-mediated proliferation check, and gradual de-vacuolation within the avascular and compression-loaded intervertebral disc. These results suggest that the notochord vacuoles are active and versatile organelles for both embryonic notochord and postnatal nucleus pulposus, and may provide novel information on intervertebral disc degeneration to guide cell-based regeneration.

Study of the Clinical Outcome between Traumatic and Degenerative (non-traumatic) Meniscal Tears after Arthroscopic Surgery: A 4-Years Follow-up Study.

INTRODUCTION: The meniscus is a biconcave fibrocartilage in the knee joint interpose between the femoral condyles and tibial plateau; the meniscus has functions in load bearing, load transmission, shock absorption joint stability, joint lubrication, and joint congruity. AIM: The aim of this study is to provide orthopeadic surgeon a base of reference in the choice of the optimal course of management for meniscal tears. MATERIALS AND METHODS: One hundred and seventeen patients met the criteria of inclusion for the present study. Patients were divided in two groups T and NT according to the presence of distinct previous traumatic events to the knees. Two subgroups were formed in each groups T and NT respectively at a mean follow up of 1 and 4 years. Postoperative clinical outcome were assessed using Lysholm scores and Rand SF-36 survey. RESULTS: One hundred and seventeen patients were included in the present study with 60(51.28%) patients in the traumatic group and 57(48.71%) in the degenerative group. 95(81.19%) patients in total were satisfied with their health status at end of follow up. The mean value of Lysholm scores at 1 year were respectively 85.25±8.78 for traumatic group and 86.38±12.14 for non-traumatic group and at 4 years were respectively 92.63±7.31 for traumatic group and 72.90±20.77 for non-traumatic group. According to Rand SF-36 health, traumatic group showed better improvements compare to non-traumatic group between 1 and 4 years after arthroscopic meniscus surgery. CONCLUSION: A total of 95(81.19%) patients in total were satisfied with their health status at follow up, however, we found that arthroscopy as a treatment for meniscal tear have a relatively better mid-term clinical outcome for traumatic meniscal tears compare to non-traumatic/degenerative meniscal tears.

Transplantation of CXCR4 Overexpressed Mesenchymal Stem Cells Augments Regeneration in Degenerated Intervertebral Discs.

SDF-1/CXCR4 chemotaxis signals play important roles in regulating the stem cell-based tissue regeneration. The aim of this research is to evaluate whether high expression of CXCR4 enhances the migration of mesenchymal stem cells (MSCs) and increases the efficiency of intervertebral disc (IVD) regeneration. MSCs overexpressing CXCR (CXCR4-MSC) were created by lentiviral-CXCR4-vect transfection, labeled with SPIO, and transplanted into rabbit degenerative IVD induced by annulus puncture. X-ray and T2-weighted MR images of the spine were obtained at 0, 8, and 16 weeks post-transplantation. The transplanted stem cells were traced by both MR imaging and Prussian blue staining. The stem cell-based IVD degeneration was evaluated by quantifying the expression of aggrecan and type II collagen. The in vitro chemotaxis test was performed to study the migration of CXCR4-MSCs to the supplement of SDF-1. The CXCR4-overexpressing MSCs stably elevated the expression of CXCR4 and increased the migration to SDF-1. The SPIO-labeled CXCR4-MSC could be detected within the IVD by MRI till 16 weeks post-transplantation. Prussian blue staining evidenced more SPIO-positive cells within the IVD transplanted with CXCR4-MSCs. Compared to the control group, loss of disc height was slowed while the mRNA expression of aggrecan and type II collagen was increased by MSC transplantation, especially in the IVD supplemented with CXCR4-MSCs. CXCR4 overexpression promoted MSC retention within the IVD and enhanced the stem cell-based IVD regeneration. The SDF-1/CXCR4 chemotaxis signals might help provide a new perspective to understand stem cell migration and infiltration within the degenerated IVD.

Labeling and tracing of bone marrow mesenchymal stem cells for tendon-to-bone tunnel healing.

PURPOSE: To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) on tendon-to-bone tunnel healing and provide experimental evidence for labeling and tracing of stem cells. METHODS: Rat BMSCs were harvested using the adherence separation technique and labeled by super paramagnetic iron oxide (SPIO) and 1,1-Dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (Dil) particles. Thirty-nine male Sprague-Dawley (SD) rats aged 8 weeks were randomly divided into two groups: experimental (n = 21) and control (n = 18). Rats from the experimental group were injected with SPIO- and Dil-labeled BMSCs and Pluronic F-127, and rats from the control group were only injected with Pluronic F-127. At 2, 4, and 8 weeks after surgery, biomechanical analysis was performed to evaluate tendon-to-bone tunnel healing. The transplanted BMSCs were observed by fluorescence microscope at 2, 4, and 8 weeks after surgery and traced by magnetic resonance (MR) imaging at 0, 3, and 7 days after surgery. RESULTS: BMSCs were labeled effectively by SPIO and Dil particles. At 2, 4, and 8 weeks after surgery, Dil-labeled cells were observed at tendon-bone interface by fluorescence microscope. In the experimental group, no obvious signal changes of tendon-bone interface were observed by MR imaging. The maximum biomechanical pull-out strength was not statistically different between experimental and control groups at 2 weeks, but significantly higher in the experimental group at 4 and 8 weeks after surgery (P < 0.05). CONCLUSION: The present study indicated that the transplanted BMSCs could promote tendon-to-bone tunnel healing at 4-8 weeks postoperatively. Dil- and SPIO-labeled transplanted BMSCs distributed at the tendon-bone interface and might play a role in promoting tendon-to-bone tunnel healing, which may be translated into practical cytotherapy for patients those who need earlier rehabilitation for ligament reconstruction surgery in clinic.

Coumestrol promotes proliferation and osteoblastic differentiation in rat bone marrow stromal cells.

Although the effects of coumestrol on osteoblasts and osteoclasts can be summarized as increasing the bone density and preventing bone resorption, direct and detailed effects of coumestrol on bone marrow stromal cells remain obscure. In the present study, the effects of coumestrol on proliferation and osteoblastic differentiation of rat bone marrow stromal cells (BMSCs) have been investigated; the regulative effect of coumestrol on BMSCs and skeletal system has also been discussed. The results showed that treatment with coumestrol increased cellular activities (analyzed by MTT assay), alkaline phosphatase (ALP), type I collagen and osteocalcin (OCN) activity as well as the protein and gene expression of OPG, gene expression ratio of OPG/RANKL and gene expression of estrogen receptor alpha(ERalpha). These results demonstrate that phytoestrogen coumestrol has a direct enhancing effect on the proliferation and osteogenic differentiation of bone marrow stromal cells, which would lead to stimulation of bone formation, and it can also protect the whole skeletal system by regulating OPG/RANKL expression, and these effects may be mediated by ERalpha.