YBX1 promotes type H vessel-dependent bone formation in an m5C-dependent manner.

RNA-binding proteins (RBPs) interact with RNA and ubiquitously regulate RNA transcripts during their life cycle, playing a fundamental role in the progression of angiogenesis-related diseases. In the skeletal system, endothelium-dependent angiogenesis is indispensable for bone formation. However, the role of RBPs in endothelium-dependent bone formation is unclear. Here, we show that RBP-Y-box-binding protein 1 (YBX1) was strongly reduced in the bone vasculature of ovariectomy (OVX) mice. Endothelial cell-specific deletion of Ybx1 impaired CD31-high, endomucin-high (CD31hiEMCNhi) endothelium morphology and resulted in low bone mass whereas Ybx1 overexpression promoted angiogenesis-dependent osteogenesis and ameliorated bone loss. Mechanistically, YBX1 deletion disrupted CD31, EMCN, and bone morphogenetic protein 4 (BMP4) stability in an m5C-dependent manner and blocked endothelium-derived BMP4 release, thereby inhibiting osteogenic differentiation of bone mesenchymal stromal cells. Administration of recombinant BMP4 protein restored impaired bone formation in Ybx1 deletion mice. Tail vein injection of CD31-modified polyethylene glycol-poly (lactic-co-glycolic acid) carrying sciadopitysin, a natural YBX1 agonist, pharmacologically partially reversed CD31hiEMCNhi vessels' decline and improved bone mass in both OVX and aging animals. These findings demonstrated the role of RBP-YBX1 in angiogenesis-dependent bone formation and provided a therapeutic approach for ameliorating osteoporosis.

The Diagnostic and Prognostic Value of Synovial Fluid Analysis in Joint Diseases.

Liquid biopsy is an emergent test method for the diagnosis and prognosis in the clinic. Joint fluid, also known as synovial fluid, contains a variety of bioactive constituents that can be selectively detected and further evaluated in a convenient fashion. Therefore, synovial fluid analysis functions as a specific form of liquid biopsy and plays a vital role in numerous joint diseases. In spite of the component analysis of aspirated synovial fluid beingconsidered as the gold standard for diagnosis of joint infections, biopsy of joint fluid benefits the initial diagnosis and long-term prognosis of degenerative, inflammatory, autoimmune, traumatic, congenital, and even neoplastic joint diseases. The convenience and accuracy for disease evaluation are significantly elevated as a result of the combination of synovial fluid analysis and other novel clinical technologies. In this review, we shed light on the latent role of synovial fluid in the diagnosis and prognosis of articular diseases and proposed future prospects for relevant research in this field.

Valid and reliable diagnostic performance of dual-energy CT in anterior cruciate ligament rupture.

OBJECTIVES: To determine whether dual-energy CT (DECT) can be used to accurately and reliably detect anterior cruciate ligament (ACL) rupture. MATERIALS AND METHODS: Participants with unilateral ACL rupture were prospectively enrolled, and the bilateral knees were scanned by DECT. A tissue-specific mapping algorithm was applied to improve the visualization of the ACLs. The 80-keV CT value, mixed-keV CT value, electron density (Rho), and effective atomic number (Zeff) were measured to quantitatively differentiate torn ACLs from normal ACLs. MRI and arthroscopy served as the reference standards. RESULTS: Fifty-one participants (mean age, 27.0 ± 8.7 years; 31 men) were enrolled. Intact and torn ACLs were explicitly differentiated on color-coded DECT images. The 80-keV CT value, mixed-keV CT value, and Rho were significantly lower for the torn ACLs than for the intact ACLs (p < 0.001). The optimal cutoff values were an 80-keV CT value of 61.8 HU, a mixed-keV CT value of 60.9 HU, and a Rho of 51.8 HU, with AUCs of 98.0% (95% CI: 97.0-98.9%), 99.2% (95% CI: 98.6-99.7%), and 99.8% (95% CI: 99.6-100.0%), respectively. Overall, DECT had almost perfect reliability and validity in detecting ACL integrity (sensitivity = 97.1% [95% CI: 88.1-99.8%]; specificity = 98.0% [95% CI: 89.5-99.9%]; PPV = 98.0% [95% CI: 93.0-99.8%]; NPV = 97.1% [95% CI: 91.7-99.4%]; accuracy = 97.5% [95% CI: 94.3-99.2%]). There was no evidence of a difference between MRI and DECT in the diagnostic performance (p > 0.99). CONCLUSION: DECT has excellent diagnostic accuracy and reliability in qualitatively and quantitatively diagnosing ACL rupture. CLINICAL RELEVANCE STATEMENT: DECT could validly and reliably diagnose ACL rupture using both qualitative and quantitative methods, which may become a promising substitute for MRI to evaluate the integrity of injured ACLs and the maturity of postoperative ACL autografts. KEY POINTS: • On color-coded DECT images, an uncolored ACL was a reliable sign for qualitatively diagnosing ACL rupture. • The 80-keV CT value, mixed-keV CT value, and Rho were significantly lower for the torn ACLs than for the intact ACLs, which contributed to the quantitative diagnosis of ACL rupture. • DECT had an almost perfect diagnostic performance for ACL rupture, and diagnostic capability was comparable between MRI and DECT.

Perlecan: Roles in osteoarthritis and potential treating target.

Osteoarthritis (OA) is the most common joint disease, affecting hundreds of millions of people globally, which leads to a high cost of treatment and further medical care and an apparent decrease in patient prognosis. The recent view of OA pathogenesis is that increased vascularity, bone remodeling, and disordered turnover are influenced by multivariate risk factors, such as age, obesity, and overloading. The view also reveals the gap between the development of these processes and early stage risk factors. This review presents the latest research on OA-related signaling pathways and analyzes the potential roles of perlecan, a typical component of the well-known protective structure against osteoarthritic pericellular matrix (PCM). Based on the experimental results observed in end-stage OA models, we summarized and analyzed the role of perlecan in the development of OA. In normal cartilage, it plays a protective role by maintaining the integrin of PCM and sequesters growth factors. Second, perlecan in cartilage is required to not only activate vascular epithelium growth factor receptor (VEGFR) signaling of endothelial cells for vascular invasion and catabolic autophagy, but also for different signaling pathways for the catabolic and anabolic actions of chondrocytes. Finally, perlecan may participate in pain sensitization pathways.

Eccentrically widened bone tunnels after all-inside anterior cruciate ligament reconstruction: a computed tomography and three-dimensional model-based analysis.

PURPOSE: To evaluate the extent of tunnel widening after anterior cruciate ligament reconstruction (ACLR) using the all-inside technique and to establish its correlation with patient-reported clinical outcomes and femoral graft bending angle (GBA). METHODS: Tunnel widening was evaluated using computed tomography (CT)-based three-dimensional (3D) models, and the femoral GBA was directly measured on CT images using the Picture Archiving and Communication System (PACS) software. Clinical follow-up was routine procedure, and patient-reported clinical outcomes mainly included International Knee Documentation Committee (IKDC), Lysholm, and Knee Injury and Osteoarthritis Outcome Scores (KOOS) scores, and subjective knee stability assessment. RESULTS: Fifty-two patients received standard all-inside ACLR, with a median follow-up of 6 months. Reconstructed anterior cruciate ligaments (ACLs) were scanned during the first 3 days and 6 months after surgery. On both the femoral and tibial sides, bone tunnels were most significantly enlarged at the articular aperture segment; the femoral tunnel was 9.2 ± 1.3 mm postoperatively and was significantly enlarged by 32% to a mean tunnel diameter of 12.1 ± 2.0 mm at 6 months after surgery. Moreover, the extent of tunnel enlargement gradually decreased as the measured levels approached those of the bone cortex. The femoral tunnel center was shifted into the anterior and distal direction, and the tibial tunnel center was shifted into the posterior and lateral direction. Additionally, the mean femoral GBA was 105.9° ± 8.1° at the 6-month follow-up. Tunnel enlargement and GBA were not significantly correlated with patient-reported outcomes. CONCLUSIONS: Femoral and tibial tunnels were significantly greater and eccentrically shifted at the 6-month follow-up after all-side ACLR. However, the extent of tunnel widening does not markedly affect the short-term clinical outcomes. Meanwhile, the femoral GBA was not significantly correlated with femoral tunnel widening or patient-reported outcomes. Although the tunnel widening following all-inside ACLR was not associated with clinical outcomes, it potentially caused difficulties in revision ACLR. LEVEL OF EVIDENCE: Level IV.

Exosomes in osteoarthritis: Updated insights on pathogenesis, diagnosis, and treatment.

Osteoarthritis (OA) has remained a prevalent public health problem worldwide over the past decades. OA is a global challenge because its specific pathogenesis is unclear, and no effective disease-modifying drugs are currently available. Exosomes are small and single-membrane vesicles secreted via the formation of endocytic vesicles and multivesicular bodies (MVBs), which are eventually released when MVBs fuse with the plasma membrane. Exosomes contain various integral surface proteins derived from cells, intercellular proteins, DNAs, RNAs, amino acids, and metabolites. By transferring complex constituents and promoting macrophages to generate chemokines and proinflammatory cytokines, exosomes function in pathophysiological processes in OA, including local inflammation, cartilage calcification and degradation of osteoarthritic joints. Exosomes are also detected in synovial fluid and plasma, and their levels continuously change with OA progression. Thus, exosomes, specifically exosomal miRNAs and lncRNAs, potentially represent multicomponent diagnostic biomarkers for OA. Exosomes derived from various types of mesenchymal stem cells and other cell or tissue types affect angiogenesis, inflammation, and bone remodeling. These exosomes exhibit promising capabilities to restore OA cartilage, attenuate inflammation, and balance cartilage matrix formation and degradation, thus demonstrating therapeutic potential in OA. In combination with biocompatible and highly adhesive materials, such as hydrogels and cryogels, exosomes may facilitate cartilage tissue engineering therapies for OA. Based on numerous recent studies, we summarized the latent mechanisms and clinical value of exosomes in OA in this review.

The top 100 most-cited articles on exercise therapy for sarcopenia: A bibliometric analysis.

Objective: Vast quantities of literature regarding the applications of exercise therapy for sarcopenia have been published. The main objective of this study is to determine the top 100 most-cited articles and analyze their bibliometric characteristics. Design: This study reports a bibliometric analysis via a systematic search of the academic literature regarding the applications of exercise therapy for sarcopenia. Methods: All databases in the Web of Science were searched with the following strategy: term search (TS) = (exercise* OR training OR "physical activit*") AND TS = (sarcopenia) on 25 February 2022. The results were presented in descending order by their total citations. The list of the top 100 articles was finally determined by negotiation of two independent researchers. Results: The top 100 articles were published between 1993 and 2020. More than half of the articles (n = 54) were published during the decade 2006-2015. Total citations of the top 100 articles ranged from 155 to 1,131 with a median of 211.5. The average of annual citations was constantly increasing with year (P < 0.05). The most studied exercise therapy is strength/resistance training, with about 71% articles had discussed about it. The top 100 articles were from 54 different journals, and the Journal of Applied Physiology was the journal that contributed the most articles (n = 8). A total of 75 different first corresponding authors from 15 countries made contributions to the top 100 list. Luc J.C. van Loon from the Maastricht University in the Netherlands published the most articles (n = 5) as the first corresponding author. Most articles (87%) were from North America (58%) and Europe (29%), while the United States as a country contributed over half of the articles (51%). Conclusion: Our study determined the top 100 most-cited articles on exercise therapy for sarcopenia and analyzed their bibliometric characteristics, which may provide a recommended list for researchers in this field and pave the way for further research.

All-Inside Anterior Cruciate Ligament Reconstruction: A Review of Advance and Trends.

Anterior cruciate ligament (ACL) injury is a common disease in orthopedics and mostly occurs as a noncontact injury in athletes. Patients' knee joint stability, which is crucial to their athletic ability, cannot be restored through conservative treatment; it can only be restored through ACLR (ACL reconstruction) surgery. The surgical techniques of ACLR are constantly evolving, from bone tendon bone (BTB) grafting combined with interface screw fixation to hamstring tendon autograft or allogeneic tendon and of suspension device constructs. In particular, the currently prevalent all-inside technique featuring good cosmetic results and quick recovery of early functions not only ensures the stable fixation of grafts but also reduces surgical trauma. This review compares the advantages and disadvantages of different aspects of all-inside ACLR, including graft selection and preparation, bone socket reconstruction, fixation methods, and surgical technique effects and limitations. It has been found that the all-inside technique excels both anatomically and clinically but still requires further development. Besides, it has some limitations, and high-quality randomized controlled trials are still required to compare the long-term effects of the all-inside technique and other ACLR techniques.

Mitochondrial Quality Control in Sarcopenia: Updated Overview of Mechanisms and Interventions.

Sarcopenia is a common geriatric disorder characterized by decreased muscle strength, low muscle mass and poor physical performance. This aging-related skeletal muscle deterioration leads to adverse outcomes and severely impairs the quality of life of patients. The accumulation of dysfunctional mitochondria with aging is an important factor in the occurrence and progression of sarcopenia. Mitochondrial quality control (MQC) fundamentally ensures the normal mitochondrial functions and is comprised of four main parts: proteostasis, biogenesis, dynamics and autophagy. Therefore, any pathophysiologic factors compromising the quality control of homeostasis in the skeletal muscle may lead to sarcopenia. However, the specific theoretical aspects of these processes have not been fully elucidated. Current therapeutic interventions using nutritional and pharmaceutical treatments show a modest therapeutic efficacy; however, only physical exercise is recommended as the first-line therapy for sarcopenia, which can ameliorate skeletal muscle deficiency by maintaining the homeostatic MQC. In this review, we summarized the known mechanisms that contribute to the pathogenesis of sarcopenia by impairing normal mitochondrial functions and described potential interventions that mitigate sarcopenia through improving MQC.

G Protein-Coupled Receptors in Osteoarthritis: A Novel Perspective on Pathogenesis and Treatment.

G protein-coupled receptors (GPCRs) are transmembrane receptor proteins that trigger numerous intracellular signaling pathways in response to the extracellular stimuli. The GPCRs superfamily contains enormous structural and functional diversity and mediates extensive biological processes. Until now, critical roles have been established in many diseases, including osteoarthritis (OA). Existing studies have shown that GPCRs play an important role in some OA-related pathogenesis, such as cartilage matrix degradation, synovitis, subchondral bone remodeling, and osteophyte formation. However, current pharmacological treatments are mostly symptomatic and there is a paucity of disease-modifying OA drugs so far. Targeting GPCRs is capable of inhibiting cartilage matrix degradation and synovitis and up-regulating cartilage matrix synthesis, providing a new therapeutic strategy for OA. In this review, we have comprehensively summarized the structures, biofunctions, and the novel roles of GPCRs in the pathogenesis and treatment of OA, which is expected to lay the foundation for the development of novel therapeutics against OA. Even though targeting GPCRs may ameliorate OA progression, many GPCRs-related therapeutic strategies are still in the pre-clinical stage and require further investigation.

Effects of Platelet-Rich Plasma and Bone Marrow Mesenchymal Stem Cells on Meniscal Repair in the White-White Zone of the Meniscus.

OBJECTIVE: To investigate the role of autologous platelet-rich plasma (PRP) on the repair of meniscal white-white zone injury through promoting the proliferation of canine bone marrow-derived mesenchymal stem cells (BMSCs). METHODS: A total of 24 beagle dogs were selected to construct meniscal white-white zone injury models in both lateral knee joints. All subjects were divided into four groups: control, BMSCs, PRP, and PRP + BMSCs. Immunohistochemistry was applied in the expression detection of type I and type II collagens. HE staining and methylene blue staining were performed to observe the injury of cartilage of lateral femoral condyle in each group. ELISA was used to detect the osteopontin (OPN) content in cartilage of lateral femoral condyle. HE staining and magnetic resonance imaging (MRI) were used to observe the healing of meniscus in each group. Outcome measures include the expression of OPN in the synovial fluid of knee joint, the expression of type I collagen and type II collagen, the healing of meniscus injury, and the damage degree of lateral femoral condyle cartilage. RESULTS: Compared with the control group, the expressions of type I and type II collagens were enhanced in the PRP group and the PRP + BMSCs group. Compared with 1 week before modeling, the expression of OPN was elevated in the control group and the BMSCs group at 3 weeks after modeling. There were no significant differences in the above indicators between the PRP group and the PRP + BMSCs group. According to MRI and pathological section after HE staining, meniscal healing in the PRP group and the PRP + BMSCs group was significantly improved as compared to that of the control group and the BMSCs group (all P < 0.05), and there was no significant difference between the PRP group and the PRP + BMSCs group (P > 0.05). All subjects were divided into the non-healing group and the healing group in accordance with the HE staining results in previous experiment. The injury of cartilage of lateral femoral condyle was significantly heavier in the non-healing group than that in the healing group. CONCLUSION: The application of PRP alone or in combination with BMSCs could promote the clinical healing rate of meniscal white-white zone injury.

Mouse models of sarcopenia: classification and evaluation.

Sarcopenia is a progressive and widespread skeletal muscle disease that is related to an increased possibility of adverse consequences such as falls, fractures, physical disabilities and death, and its risk increases with age. With the deepening of the understanding of sarcopenia, the disease has become a major clinical disease of the elderly and a key challenge of healthy ageing. However, the exact molecular mechanism of this disease is still unclear, and the selection of treatment strategies and the evaluation of its effect are not the same. Most importantly, the early symptoms of this disease are not obvious and are easy to ignore. In addition, the clinical manifestations of each patient are not exactly the same, which makes it difficult to effectively study the progression of sarcopenia. Therefore, it is necessary to develop and use animal models to understand the pathophysiology of sarcopenia and develop therapeutic strategies. This paper reviews the mouse models that can be used in the study of sarcopenia, including ageing models, genetically engineered models, hindlimb suspension models, chemical induction models, denervation models, and immobilization models; analyses their advantages and disadvantages and application scope; and finally summarizes the evaluation of sarcopenia in mouse models.

Sphingosine 1-phosphate and osteoporosis: pathophysiology and therapeutic aspects-a narrative review.

Sphingosine 1-phosphate (S1P) regulates many cellular functions, such as differentiation, proliferation, migration, morphogenesis, cytoskeletal organization, adhesion, tight junction assembly, apoptosis and the localization of different cell types. S1P also controls the migration of osteoclast precursors between the blood and bone, and it keeps osteoclast precursors away from bone surfaces to reduce bone degradation, thus preventing bone decay. Osteoporosis is a systemic bone disease that predisposes patients to bone fracture due to decreased bone density and quality, disrupted bone microarchitecture, and increased bone fragility. As the global elderly population increases, the incidence of osteoporosis will greatly increase, and the associated adverse consequences will become more serious. S1P plays an important role in homeostasis, and disruption of the balance between osteoblasts and osteoclasts may induce osteoporosis. A high frequency of osteoporotic fracture is associated with increased plasma S1P levels. Studies have shown that S1P is an important therapeutic target in osteoporosis because it controls the migration of osteoclast precursors, vigorously maintains the bone mineralization process, and is a critical regulator of osteoclastogenesis. Improved understanding of the functional roles and molecular mechanisms of S1P in bone turnover could facilitate the discovery of novel targets for the treatment of osteoporosis. This review provides a critical discussion of the role of S1P in osteoporosis and treatments.

Circular RNA in osteoarthritis: an updated insight into the pathophysiology and therapeutics.

Osteoarthritis (OA) is a common joint disease that mainly results in chronic pain, stiffness and dysfunction in elderly individuals. The molecular mechanisms in the pathogenesis of OA are still unclear, and available treatments are unable to slowdown the development of OA or reverse the tissue damage. Circular RNAs (circRNAs), a novel type of non-coding RNA, are ubiquitous, stable, evolutionally conserved, tissue-specific and functional. An increasing number of studies have revealed that many circRNAs are differentially expressed in OA-affected joint tissues and engage in the pathogenesis of OA by functioning as miRNA sponges. In this review, we briefly introduce the biogenesis, characteristics and functions of circRNAs, and shed light on the important role of circRNAs in the occurrence and progression of OA and their potential diagnostic and therapeutic value in this disease based on the research over the last five years.

Possible sarcopenia: early screening and intervention-narrative review.

Sarcopenia is a new geriatric syndrome that has become a heavily researched topic, and it is a potential risk factor for weakness, disability, and death in elderly people. As the world's population ages, the incidence of sarcopenia has also increased, which has resulted in a series of health problems and in large medical costs. Although there are generally accepted diagnostic criteria for sarcopenia, the existing criteria require a comprehensive evaluation of muscle quality, muscle strength and muscle function. Most of these evaluations are time-consuming, labourious, difficult to implement, and unsuitable for large-scale population surveys. Moreover, the abilities of the elderly to undertake daily-life activities are often affected when they are diagnosed with sarcopenia. Therefore, if individuals who are likely to suffer from sarcopenia could be identified by screening at an early stage and then comprehensively evaluated, time and labour would be saved, and the detection rate would be improved. Timely intervention can be undertaken in possible sarcopenia to prevent further development of sarcopenia and strongly improve the quality of life of individuals. This study reviews the early screening and intervention of the possible sarcopenia, analyses its advantages and disadvantages and attempt to identify reliable and practical methods to reduce adverse consequences and the extent of harm.

Characterization of the Subchondral Bone and Pain Behavior Changes in a Novel Bipedal Standing Mouse Model of Facet Joint Osteoarthritis.

BACKGROUND: The subchondral bone parallels with the progression of osteoarthritis (OA). However, the biomechanical properties and histopathological changes of subchondral bone changes in the lumbar facet joint (LFJ) after long-term axial loading on the spine have not been explored. In this study, we aimed to investigate the subchondral bone histopathological changes that occur in the LFJ and pain behaviors in a novel bipedal standing mouse model. METHODS: Sixteen 8-week-old male C57BL/6 mice were randomly assigned into bipedal standing and control groups. A finite element stimulate model based on the micro-CT data was generated to simulate the von Mises stress distribution on the LFJ during different positions. The spine pain behaviors tests were analysis. In addition, the change in the subchondral bone of the LFJ was assessed by histological and immunohistochemistry staining. RESULTS: The computerized simulation of the von Mises stress distribution in the superior articular process of LFJ at the spine level 5 in the lying position increased and reached a maximum value at the bipedal standing posture. The spine pain behavior test revealed that the threshold of pressure tolerance decreased significantly in bipedal groups relative to control groups, whereas the mechanical hyperalgesia of the hind paw increased significantly in bipedal groups relative to control groups. The axial load accelerates LFJ degeneration with increased histological scores in bipedal groups. The expression of type II collagen and aggrecan (ACAN) was significantly decreased in the bipedal groups compared with the control groups, whereas the expression of MMP13 was increased. Compared with the control groups, the osteoclast activity was activated with higher TRAP-positive staining and associated with increased CD-31-positive vessels and GCRP-positive nerve ending expression in the subchondral bone of LFJ. CONCLUSION: Collectively, long-term axial loading induces the development of spine hyperalgesia in mice associate with increased osteoclast activity and aberrant angiogenesis and nerve invasion into the subchondral bone of LFJ that stimulates the natural pathological change in human LFJ OA. These results indicate that aberrant bone remodeling associate with aberrant nerve innervation in the subchondral bone has a potential as a therapeutic target in LFJ OA pain.

Caloric restriction: implications for sarcopenia and potential mechanisms.

Sarcopenia is a potential risk factor for weakness, disability and death in elderly individuals. Therefore, seeking effective methods to delay and treat sarcopenia and to improve the quality of life of elderly individuals is a trending topic in geriatrics. Caloric restriction (CR) is currently recognized as an effective means to extend the lifespan and delay the decline in organ function caused by aging. In this review, we describe the effects of CR on improving muscle protein synthesis, delaying muscle atrophy, regulating muscle mitochondrial function, maintaining muscle strength, promoting muscle stem cell (MuSC) regeneration and differentiation, and thus protecting against sarcopenia. We also summarize the possible cellular mechanisms by which CR delays sarcopenia. CR can delay sarcopenia by reducing the generation of oxygen free radicals, reducing oxidative stress damage, enhancing mitochondrial function, improving protein homeostasis, reducing iron overload, increasing autophagy and apoptosis, and reducing inflammation. However, the relationships between CR and genetics, sex, animal strain, regimen duration and energy intake level are complex. Therefore, further study of the proper timing and application method of CR to prevent sarcopenia is highly important for the aging population.

Remnant-Preserving Posterior Cruciate Ligament Reconstruction Over Remnant Fibers Using a Figure-of-Four Position and a Posterior Trans-Septal Portal.

Anatomic tunnel formation and remnant preservation are the recent trends in posterior cruciate ligament (PCL) reconstruction. However, it is difficult to observe the anatomical PCL footprint and perform the operation in the process of remnant-preserving PCL reconstruction. This study describes a single-bundle, transtibial PCL reconstruction technique with anatomic graft passage over the remnant PCL fibers. A femoral tunnel of PCL is created at 2 mm medial to the roof of the intercondylar notch and 3 mm proximal to the margin of the articular cartilage. The tibial insertion of PCL is observed using a figure-of-four position through a posterior trans-septal portal. A tibial bone tunnel is made below the distal center portion of the tibial insertion of residual PCL fibers. The graft is passed over the PCL through the tibial bone tunnel, the space between the anterior cruciate ligament (ACL) and the residual PCL fibers, to the femoral socket and is fixed by the EndoButton and screw. This technique is able to ensure a reasonable intra-articular length and optimal isometry. It has been applied in patients with PCL rupture and posterior instability of the knee joint, and no intraoperative or postoperative complications occurred. Our technology provides a valuable new treatment option for PCL rupture. Future comparative studies are needed to further clarify its beneficial effect.

Arthroscopic Treatment of Femoral Avulsion Fracture of the Posterior Cruciate Ligament in Association with Meniscus Tear.

BACKGROUND: Femoral avulsion fracture of the posterior cruciate ligament (PCL) in association with meniscus tear is extremely rare in children, and similar cases are not available in the existing literature. CASE PRESENTATION: In this paper, we present a case of a 9-year-old boy treated by an arthroscopic repair technique using two transfemoral tunnels sparing the epiphyseal plate for 8-shaped suture fixation of femoral avulsion fracture of the PCL and using the Fastfix repair system for a meniscus tear. At 3-month postoperative, the boy showed satisfactory recovery with a full range of motion of the right knee and normal muscular strength, and no complications were observed after operation. The patient had been followed up for 24 months and his final assessment demonstrated stable painless knee with excellent functional outcome. In view of this, we suggest that the "figure-of-eight" suture technique using two transfemoral tunnels sparing the epiphyseal plate can be considered a new choice for the treatment of the PCL femoral attachment avulsion, especially in skeletally immature patients. In addition, six similar cases were found in a comprehensive literature review targeting femoral avulsion fracture of the PCL. According to the relevant findings and cases studies, we proposed a new classification named "Xiangya" which might facilitate future clinical decision making.

Functional role of hedgehog pathway in osteoarthritis.

The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up-regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix-degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of HH gene is not an option for OA treatment in humans because it is not possible to delete HH in larger animals. Efficient knockdown of HH achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions.