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.

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.

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.

Clinical and imaging manifestations of primary cardiac angiosarcoma.

BACKGROUND: To investigate the CT manifestations of primary cardiac angiosarcoma. METHODS: The clinical and CT data for 9 patients with cardiac angiosarcoma were retrospectively analyzed. RESULTS: The lesions in all nine cases were located in the right atrium. In two cases, the involved lesion led downward to the tricuspid valve and right ventricle, and the dynamic cine showed that the lesion affected the opening and closing of the tricuspid valve. In three cases, the lesion involvement led to a thickened pericardium, accompanied by pericardial effusions. On CT plain scans, six patients showed homogeneous density, while three showed inhomogeneous density, two of which were associated with bleeding. On enhanced CT scans, seven patients showed heterogeneous centripetal enhancement, and some angiograms showed lesions with tortuous small blood vessels. The remaining two cases showed early stage rapid inhomogeneous enhancement. Five cases showed multiple metastatic nodules in the lungs at the time of initial diagnosis; four of these showed distinct sharp edges in multiple pulmonary nodules. CONCLUSIONS: Cardiac angiosarcoma has a predilection site and is prone to invading adjacent structures, manifesting as malignant pericardial and pleural effusions. The CT enhancement manifestations are mostly inhomogeneous and centripetal with ground-glass opacity peripheral to the intrapulmonary metastases.

Single nucleotide polymorphisms in the CD40 gene associate with the disease susceptibility and severity in knee osteoarthritis in the Chinese Han population: a case-control study.

BACKGROUND: This study explored the association between single nucleotide polymorphisms (SNPs) in the CD40 gene, rs4810485 G > T and rs1883832 C > T, as well as disease susceptibility and severity in knee osteoarthritis (KOA) in the Chinese Han population. METHOD: Peripheral venous blood was collected from 133 KOA patients (KOA group) and 143 healthy people (control group) from December 2012 to November 2013. The patients in the KOA group were classified into mild, moderate and severe groups according to disease severity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the genotypes of all subjects. Binary logistic regression analyses were performed to analyze the risk factors for KOA. RESULTS: The KOA group was significantly different from the control group in living environment (P < 0.05). The KOA group had a lower frequency of TT genotype and T allele distribution of rs4810485 G > T compared with the control group, and rs4810485 G > T TT genotype and T allele may associate with low incidence of KOA (all P < 0.05). Besides, T allele and mutant homozygous TT genotype of rs1883832 C > T increased the susceptibility to KOA. Genotype and allele distribution of rs4810485 G > T and rs1883832 C > T were significantly different among the mild, moderate and severe groups (P < 0.05). There were more patients with rs4810485 G > T GG genotype and rs1883832 C > T TT genotype in the severe group than other genotypes of these two SNPs. According to binary logistic regression analysis, rs4810485 G > T TT genotype could alleviate disease severity in KOA, rs1883832 C > T TT genotype increase the severity of KOA and living environment is an important external factor that affects KOA severity. CONCLUSIONS: These data provide evidences that rs4810485 G > T and rs1883832 C > T in the CD40 gene may be associated with disease susceptibility and severity in KOA.

Associations of dietary and serum magnesium with serum high-sensitivity C-reactive protein in early radiographic knee osteoarthritis patients.

INTRODUCTION: This study aimed to examine the associations of dietary magnesium (Mg) intake and serum Mg concentration with the high-sensitivity C-reactive protein (hsCRP) level in early radiographic knee osteoarthritis (OA) patients. METHODS: Multivariable logistic regression was used to test the associations of dietary and serum Mg with the serum hsCRP in early radiographic knee OA patients after adjustment of a number of potential confounding factors. RESULTS: A total of 936 early radiographic knee OA patients were included. A significant association between dietary Mg intake and hsCRP was observed. The multivariable-adjusted odds ratio (OR) (95% CI) for elevated hsCRP (≥3.0 mg/l) in the second, third, fourth, and fifth dietary Mg intake quintile were 0.44 (95% CI: 0.24-0.82), 0.58 (95% CI: 0.31-1.10), 0.34 (95% CI: 0.15-0.77), and 0.19 (95% CI: 0.06-0.57), respectively, compared with the lowest (first) quintile, and p for trend was 0.01. A significant association between serum Mg concentration and hsCRP was observed. The multivariable-adjusted OR (95% CI) for elevated hsCRP in the second, third, fourth, and fifth serum Mg concentration quintile were 0.63 (95% CI: 0.35-1.12), 0.83 (95% CI: 0.50-1.39), 0.53 (95% CI: 0.31-0.91), and 0.46 (95% CI: 0.25-0.85), respectively, compared with the lowest quintile, and p for trend was 0.01. CONCLUSION: The present study indicated that both dietary and serum Mg were inversely associated with serum hsCRP in early radiographic knee OA patients.

Network Meta-Analysis of Pharmacological Agents for Osteoporosis Treatment and Fracture Prevention.

BACKGROUND AND OBJECTIVE: Osteoporosis afflicts a large number of populations in the world and is featured by systemic impairment of bone mass and strength which may further trigger an increase in the risk of fragile fractures. This network meta-analysis (NMA) is designed to distinguish therapies more preferable than others with respect to efficacy and safety. METHODS: We searched the medical literature for relevant studies systematically. Both direct and indirect evidence were synthesized to compare the efficacy, described by odds ratios (OR) and 95% credible intervals (CrI). Moreover, the surface under cumulative ranking curve was calculated to rank probabilities with respect to clinical outcomes. The new non-vertebral fractures, hip and wrist fractures, and adverse events were evaluated in this NMA. RESULTS: Patients treated by alendronate, denosumab, teriparatide were associated with a reduced risk of new non-vertebral fractures compared to those treated by placebo. Alendronate, denosumab and zoledronic acid had better efficacy in preventing hip fractures. With respect to wrist fractures prevention, no significant difference was observed. Zoledronic acid exhibited significantly increased risk of adverse events than placebo, alendronate, denosumab, and raloxifene. According to SUCRA, teriparatide ranked highest in new non-vertebral fractures prevention, etidronate and denosumab balanced safety and efficacy well. CONCLUSION: In summary, teriparatide appeared to be the most efficacious drug for preventing new non-vertebral fractures, while etidronate and denosumab were preferable for balancing safety and efficacy well.

Relationship between soy milk intake and radiographic knee joint space narrowing and osteophytes.

The purpose of this study was to examine the cross-sectional association between dietary soy milk intake and the prevalence of radiographic knee joint space narrowing (JSN) and osteophytes (OST). Soy milk intake was assessed using a validated semiquantitative food frequency questionnaire and classified into three categories: never,

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.

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.

Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke.

BACKGROUND: Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. METHODS: Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. RESULTS: Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. CONCLUSION: The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.

Effect of Epimedium pubescen flavonoid on bone mineral density and biomechanical properties of femoral distal end and femoral diaphysis of passively smoking male rats.

BACKGROUND: Based on a rat model of human relatively high exposure to cigarette smoke, this study aimed to estimate whether Epimedium pubescen flavonoid (EPF) may prevent a smoke-induced decrease in bone mineral density (BMD) and weakening of the biomechanical properties of bone. METHODS: Fifty male Wistar rats were randomized into five groups: controls, passively smoking groups and passively smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive cigarette smoking was prepared by breeding male rats in a cigarette-smoking box for 4 months. Bone metabolic makers, BMD and biomechanical properties of the femoral distal end and femoral diaphysis were examined. RESULTS: Exposure to cigarette smoke decreased the BMD, affected bone turnover (inhibited bone formation and stimulated its resorption) and weakened the biomechanical properties of the femur at its distal end and diaphysis. EPF supplementation during cigarette smoke exposure prevented the decrease in BMD, accelerated bone turnover and weakened the biomechanical properties of bone. CONCLUSION: Our data suggest that EPF supplementation can prevent the adverse effects of smoke exposure on BMD and biomechanical properties by inhibiting bone turnover and preventing bone resorption, and in this way it can decrease the risk of bone fractures.

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.

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.

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.

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.

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.