Matrix stiffness-mediated tenogenesis of tendon stem/progenitor cells via integrin-αm for tendon regeneration.

Tendon injuries, commonly associated with sports activities, pose significant challenges in terms of treatment and recovery due to limited tendon regeneration and the formation of proliferative scars. Stem cell-based therapy has shown promising application, but there are still challenges. Physical and biological cues are instrumental in guiding stem cell differentiation and maturation. This study focuses on exploring the effects of matrix biomechanics on tendon stem/progenitor cells (TSPCs) differentiation. We fabricated polydimethylsiloxane (PDMS) substrates with different elastic modulus to mimic the mechanical characteristics of healthy tendons. A tissue-engineered culture system was developed for tenogenesis, and pre-differentiated tissue-engineered tendons were transplanted in vivo to assess their efficacy in regenerating patella tendon injuries. Furthermore, we demonstrated that the biomechanical stimuli activated the integrin-αm to enhance the tenogenesis capacity of TSPCs. Our findings highlight the importance of biomechanics in tendon tissue engineering and provide a novel perspective for enhancing tendon regeneration.

The potential function of KIF17 in large yellow croaker (Larimichthys crocea) spermatid remodeling: molecular characterization and expression pattern during spermiogenesis.

KIF17, which belongs to the kinesin-2 protein family, plays an indispensable role in mammalian spermiogenesis. However, the role of KIF17 in fish spermatid remodeling during spermiogenesis remains poorly understood. Therefore, we aimed to study the role of KIF17 in spermatid remodeling during Larimichthys crocea (L. crocea) spermiogenesis. The kif17 cDNA sequence, 3247 bp in length, was cloned from L. crocea testis, which consisted of a 347-bp 5'-untranslated region (UTR), 413-bp 3' -UTR, and 2487-bp open reading frame. Bioinformatic analyses revealed that KIF17 obtained from L. crocea (Lc-KIF17) exhibited a high sequence identity compared with those from other teleosts and possessed the structural features of other kinesin-2 proteins. Based on structural similarity, we speculate that the role of Lc-KIF17 may be similar to that of KIF17 in other animals. Lc-kif17 mRNA was diffusely expressed in L. crocea tissues and was highly expressed in the testis, especially at stage IV testicular development. Immunofluorescence analysis revealed that Lc-KIF17 signals colocalized with ß-tubulin signals and migrated from the perinuclear cytoplasm to the side of the nucleus where the tail forms during spermiogenesis. These findings revealed that KIF17 may be involved in L. crocea spermiogenesis. In particular, KIF17 may participate in spermatid remodeling by interacting with perinuclear microtubules during L. crocea spermiogenesis. Collectively, this study contributes to an improved understanding of the mechanism underlying L. crocea spermiogenesis and provides a basis for further research on L. crocea reproduction and development.

Effects of acute low temperature stress on the hormones and gene expression of glucocorticoid receptor of large yellow croaker Larimichthys crocea.

The neuroendocrine system of fish responds to low temperature via regulating hormones. To explore the adaptability of Larimichthys crocea to low temperature, the levels of the plasma cortisol, thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), total cholesterol (TC), and glucose were determined after exposure to low temperature and during subsequent rewarming. Furthermore, the mRNA expression of the glucocorticoid receptor (GR) gene was analyzed under the stress. We found that the levels of the plasma cortisol, TSH, T3, glucose, and TC increased under the low temperature stress, suggesting that elevated hormones may be conducive to promoting the mobilization of the glucose and lipid in L. crocea exposed to low temperature. During the rewarming period, the plasma cortisol level decreased, whereas the T3 level was still significantly higher than that in the control group. Notably, the plasma T4 level was unaffected by the temperature changes. Furthermore, the sequence alignment and phylogenetic tree analysis revealed that the GR protein of L. crocea had high homology and a similar protein structure with those from other teleosts. Under the low temperature stress, the GR mRNA expression increased in the brain and head kidney, whereas it basically returned to the control level following rewarming. These findings revealed the changes of the hormones and the potential function of the GR gene in L. crocea following exposure to low temperature, providing some insights into breeding low temperature-resistant varieties of L. crocea.

The relationship between substrate topography and stem cell differentiation in the musculoskeletal system.

It is well known that biomaterial topography can exert a profound influence on various cellular functions such as migration, polarization, and adhesion. With the development and refinement of manufacturing technology, much research has recently been focused on substrate topography-induced cell differentiation, particularly in the field of tissue engineering. Even without biological and chemical stimuli, the differentiation of stem cells can also be initiated by various biomaterials with different topographic features. However, the underlying mechanisms of this biological phenomenon remain elusive. During the past few decades, many researchers have demonstrated that cells can sense the topography of materials through the assembly and polymerization of membrane proteins. Following the activation of RHO, TGF-b or FAK signaling pathways, cells can be induced into various differentiation states. But these signaling pathways often coincide with canonical mechanical transduction pathways, and no firm conclusion has been reached among researchers in this field on topography-specific signaling pathways. On the other hand, some substrate topographies are reported to have the ability to inhibit differentiation and maintain the 'stemness' of stem cells. In this review, we will summarize the role of topography in musculoskeletal system regeneration and explore possible topography-related signaling pathways involved in cell differentiation.

Transcriptome and physiology analysis identify key metabolic changes in the liver of the large yellow croaker (Larimichthys crocea) in response to acute hypoxia.

The large yellow croaker (Larimichthys crocea) is one of the most important marine economic fish in the southeast coast of China. However, hypoxia stress become a major obstacle to the benign development of L. crocea industry. To understand the energy metabolism mechanism adapted to hypoxia, we analyzed the transcriptome and physiology of L. crocea liver in response to hypoxia stress for different durations. We obtained 243,756,080 clean reads, of which 83.38% were successfully mapped to the reference genome of L. crocea. The heat map analysis showed that genes encoding enzymes involved in glycolysis/gluconeogenesis were significantly upregulated at various time points. Moreover, genes encoding enzymes related to the citrate cycle, oxidative phosphorylation, and amino acid metabolism were significantly downregulated at 6 and 24 h, but upregulated at 48 and 96 h. The change of liver in physiology processes, including respiratory metabolism, and activities of the carbohydrate metabolism enzymes showed a similar trend. The results revealed that the respiratory metabolism of L. crocea was mainly anaerobic within 24 h of hypoxia stress, and aerobic metabolism was dominant after 24 h. Carbohydrate metabolism plays a crucial role in energy supply and amino acid metabolism is an important supporting character to cope with acute hypoxia stress. There was no significant change in lipid utilization under short-term acute stress. This study increases our understanding of the energy metabolism mechanism of the hypoxia response in fish and provides a useful resource for L. crocea genetics and breeding.

Small molecule therapeutics for inflammation-associated chronic musculoskeletal degenerative diseases: Past, present and future.

Inflammation-associated chronic musculoskeletal degenerative diseases (ICMDDs) like osteoarthritis and tendinopathy often results in morbidity and disability, with consequent heavy socio-economic burden. Current available therapies such as NSAIDs and glucocorticoid are palliative rather than disease-modifying. Insufficient systematic research data on disease molecular mechanism also makes it difficult to exploit valid therapeutic targets. Small molecules are designed to act on specific signaling pathways and/or mechanisms of cellular physiology and function, and have gradually shown potential for treating ICMDDs. In this review, we would examine and analyze recent developments in small molecule drugs for ICMDDs, suggest possible feasible improvements in treatment modalities, and discuss future research directions.

Cross Pin Versus Interference Screw for Femoral Graft Fixation in Hamstring Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis of Clinical Outcomes.

PURPOSE: To compare the effectiveness of a cross pin and interference screw for femoral graft fixation in primary anterior cruciate ligament reconstruction (ACLR) and provide an appropriate reference for orthopaedic surgeons. METHODS: The Medline, Cochrane Library, Web of Science, Scopus, and PubMed databases were searched in March 2016, and comparative trials using cross-pin and interference screw devices for femoral graft fixation in primary hamstring ACLR with clinical outcome measurements were included in the review. Trials with no controlled groups, hybrid fixation, no clinical outcomes, or follow-up of less than 1 year were excluded. The quality of the included studies was assessed with the Cochrane Back Review Group 12-item scale. Abstracted data were pooled with fixed or random effects depending on the detected heterogeneity. The outcome measures were the scoring system and physical examination findings, including the Lysholm score, International Knee Documentation Committee score or grade, Tegner score, negative Lachman test, negative pivot-shift test, and instrumented side-to-side anterior-posterior laxity difference. RESULTS: All the studies reviewed were of prospective design. Within the cross-pin group, patients who underwent hamstring ACLR showed a significantly smaller instrumented side-to-side anterior-posterior laxity difference when compared with interference screw fixation (weighted mean difference, 0.38 mm [95% confidence interval, 0.08-0.67 mm]; P = .01), whereas the results of a negative Lachman test and negative pivot-shift test were comparable. Outcomes regarding the scoring system did not reach a significant difference between the 2 groups. CONCLUSIONS: The statistically decreased instrumented side-to-side anterior-posterior laxity difference achieved by cross-pin transfixation appears to be of limited clinical significance when compared with interference screw fixation in primary hamstring ACLR. Clinically, the performance of cross-pin devices did not show a significant advantage over that of the interference screw for femoral graft fixation in hamstring ACLR. LEVEL OF EVIDENCE: Level II.

Effects of fasting on the activities and mRNA expression levels of lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and fatty acid synthetase (FAS) in spotted seabass Lateolabrax maculatus.

To investigate the effects of fasting on lipid metabolism in spotted seabass muscle and liver tissues, we analyzed mRNA levels and enzyme activities of lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and fatty acid synthetase (FAS), and the relationship among fat content, mRNA level, and enzyme activity during fasting of 35 days. The results showed that expressions of all the three genes were ubiquitous. During the fasting experiment, the hepatosomatic index (HSI) and fat content of muscle and liver tissues significantly decreased before 5 days of fasting (P < 0.05). mRNA levels of LPL increased significantly after 5 days of fasting in liver and 7 days in muscle. Abundance of HSL transcripts increased significantly after 14 days of fasting in both muscle and liver. The activities of LPL and HSL presented a trend that increased firstly, decreased subsequently, and then raised again with the prolonged fasting experiment (P < 0.05). However, activities and mRNA levels of FAS decreased significantly after 1 day of fasting in both muscle and liver. Moreover, activities and mRNA levels of FAS showed a moderate correlation in muscle. These results suggested that FAS had a sooner response to fasting than LPL and HSL in both muscle and liver tissues. LPL and HSL played important roles in lipolysis mainly by increasing enzyme activities in the early stage of fasting and mRNA levels in the later stage of fasting in both muscle and liver. Our results also provided useful information on regulating muscle fat content by fasting.

Pharmacological Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification Treatment.

Calcification of soft tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured tissues. But some of them become divergent to the direction of ossification in the local pathological microenvironment, thereby representing a cellular target for pharmacological approach. We observed that HIF-2alpha (encoded by EPAS1 inclined form) signaling is markedly activated within stem/progenitor cells recruited at calcified sites of diseased human tendons and heart valves. Proinflammatory microenvironment, rather than hypoxia, is correlated with HIF-2alpha activation and promoted osteochondrogenic differentiation of tendon stem/progenitor cells (TSPCs). Abnormal upregulation of HIF-2alpha served as a key switch to direct TSPCs differentiation into osteochondral-lineage rather than teno-lineage. Notably, Scleraxis (Scx), an essential tendon specific transcription factor, was suppressed on constitutive activation of HIF-2alpha and mediated the effect of HIF-2alpha on TSPCs fate decision. Moreover, pharmacological inhibition of HIF-2alpha with digoxin, which is a widely utilized drug, can efficiently inhibit calcification and enhance tenogenesis in vitro and in the Achilles's tendinopathy model. Taken together, these findings reveal the significant role of the tissue stem/progenitor cells fate decision and suggest that pharmacological regulation of HIF-2alpha function is a promising approach for soft tissue calcification treatment.

[Progress on treatment of tendinopathy with platelet-enriched plasma].

Platelet-enriched plasma (PRP) contains high concentration of platelets and abundant growth factors, which is made by centrifuging of blood and separating of blood elements. PRP promotes tendon repair by releasing various cytokines to enhance cell proliferation, tenogenic differentiation, formation and secretion of matrix; meantime, it can reduce pain by inhibiting the expression of pain-associated molecules. A number of clinical studies demonstrated that PRP was effective in treatment of tendinopathy, including patellar tendinopathy, lateral epicondylitis and plantar fasciopathy. However, some studies did not support this conclusion, because of disparity of PRP types, therapeutic courses and injections protocols in clinical application. Based on its safety, PRP can be a choice of treatment for tendinopathy, in case other non-surgical therapies are of no effect.

[Three-dimensional parallel collagen scaffold promotes tendon extracellular matrix formation].

OBJECTIVE: To investigate the effects of three-dimensional parallel collagen scaffold on the cell shape, arrangement and extracellular matrix formation of tendon stem cells. METHODS: Parallel collagen scaffold was fabricated by unidirectional freezing technique, while random collagen scaffold was fabricated by freeze-drying technique. The effects of two scaffolds on cell shape and extracellular matrix formation were investigated in vitro by seeding tendon stem/progenitor cells and in vivo by ectopic implantation. RESULTS: Parallel and random collagen scaffolds were produced successfully. Parallel collagen scaffold was more akin to tendon than random collagen scaffold. Tendon stem/progenitor cells were spindle-shaped and unified orientated in parallel collagen scaffold, while cells on random collagen scaffold had disorder orientation. Two weeks after ectopic implantation, cells had nearly the same orientation with the collagen substance. In parallel collagen scaffold, cells had parallel arrangement, and more spindly cells were observed. By contrast, cells in random collagen scaffold were disorder. CONCLUSION: Parallel collagen scaffold can induce cells to be in spindly and parallel arrangement, and promote parallel extracellular matrix formation; while random collagen scaffold can induce cells in random arrangement. The results indicate that parallel collagen scaffold is an ideal structure to promote tendon repairing.

[Application of silk-based tissue engineering scaffold for tendon / ligament regeneration].

Tendon/ligament injury is one of the most common impairments in sports medicine. The traditional treatments of damaged tissue repair are unsatisfactory, especially for athletes, due to lack of donor and immune rejection. The strategy of tissue engineering may break through these limitations, and bring new hopes to tendon/ligament repair, even regeneration. Silk is a kind of natural biomaterials, which has good biocompatibility, wide range of mechanical properties and tunable physical structures; so it could be applied as tendon/ligament tissue engineering scaffolds. The silk-based scaffold has robust mechanical properties; combined with other biological ingredients, it could increase the surface area, promote more cell adhesion and improve the biocompatibility. The potential clinical application of silk-based scaffold has been confirmed by in vivo studies on tendon/ligament repairing, such as anterior cruciate ligament, medial collateral ligament, achilles tendon and rotator cuff. To develop novel biomechanically stable and host integrated tissue engineered tendon/ligament needs more further micro and macro studies, combined with product development and clinical application, which will give new hope to patients with tendon/ligament injury.

Novel methods to diagnose rotator cuff tear and predict post-operative Re-tear: Radiomics models.

Objective: To validated a classifier to distinguish the status of rotator cuff tear and predict post-operative re-tear by utilizing magnetic resonance imaging (MRI) markers. Methods: This retrospective study included patients with healthy rotator cuff and patients diagnosed as rotator cuff tear (RCT) by MRI. Radiomics features were identified from the pre-operative shoulder MRI and selected by using maximum relevance minimum redundancy (MRMR) methods. A radiomics model for diagnosis of RCT was constructed, based on the 3D volume of interest (VOI) of supraspinatus. Another model for the prediction of rotator re-tear after rotator cuff repair (Re-RCT) was constructed based on VOI of humerus, supraspinatus, infraspinatus and other clinical parameters. Results: The model for diagnosing the status of RCT produced an area under the receiver operating characteristic curve (AUC) of 0.989 in the training cohort and 0.979 for the validation cohort. The radiomics model for predicting Re-RCT produced an AUC of 0.923 ± 0.017 for the training dataset and 0.790 ± 0.082 for the validation dataset. The nomogram combining radiomics features and clinical factors yielded an AUC of 0.961 ± 0.020 for the training dataset and 0.808 ± 0.081 for the validation dataset, which displayed the best performance among all models. Conclusion: Radiomics models for the diagnosis of rotator cuff tear and prediction of post-operative Re-RCT yielded a decent prediction accuracy.

Gel microspheres enhance the stemness of ADSCs by regulating cell-ECM interaction.

The gel microsphere culture system (GMCS) showed various advantages for mesenchymal stem cell (MSC) expansion and delivery, such as high specific surface area, small and regular shape, extensive adjustability, and biomimetic properties. Although various technologies and materials have been developed to promote the development of gel microspheres, the differences in the biological status of MSCs between the GMCS and the traditional Petri dish culture system (PDCS) are still unknown, hindering gel microspheres from becoming a culture system as widely used as petri dishes. In the previous study, an excellent "all-in-one" GMCS has been established for the expansion of human adipose-derived MSCs (hADSCs), which showed convenient cell culture operation. Here, we performed transcriptome and proteome sequencing on hADSCs cultured on the "all-in-one" GMCS and the PDCS. We found that hADSCs cultured in the GMCS kept in an undifferentiation status with a high stemness index, whose transcriptome profile is closer to the adipose progenitor cells (APCs) in vivo than those cultured in the PDCS. Further, the high stemness status of hADSCs in the GMCS was maintained through regulating cell-ECM interaction. For application, bilayer scaffolds were constructed by osteo- and chondro-differentiation of hADSCs cultured in the GMCS and the PDCS. The effect of osteochondral regeneration of the bilayer scaffolds in the GMCS group was better than that in the PDCS group. This study revealed the high stemness and excellent functionality of MSCs cultured in the GMCS, which promoted the application of gel microspheres in cell culture and tissue regeneration.

A pathological joint-liver axis mediated by matrikine-activated CD4+ T cells.

The knee joint has long been considered a closed system. The pathological effects of joint diseases on distant organs have not been investigated. Herein, our clinical data showed that post-traumatic joint damage, combined with joint bleeding (hemarthrosis), exhibits a worse liver function compared with healthy control. With mouse model, hemarthrosis induces both cartilage degeneration and remote liver damage. Next, we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4+ T cells in peripheral blood and spleen. Deletion of CD4+ T cells reverses hemarthrosis-induced liver damage. Degeneration of cartilage matrix induced by hemarthrosis upregulates serological type II collagen (COL II), which activates CD4+ T cells. Systemic application of a COL II antibody blocks the activation. Furthermore, bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood treatment. Intra-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig models. Taken together, our study revealed a pathological joint-liver axis mediated by matrikine-activated CD4+ T cells, which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease. Intra-articular bleeding induces cartilage degradation through down-reulation of cartilage Akt pathway. During this process, the soluble COL II released from the damaged cartilage can activate peripheral CD4+ T cells, differention into Th17 cells and secretion of IL-17, which consequently induces liver impairment. Intra-articular application of sc79 (inhibitor of Akt pathway) can prevent the cartilage damage as well as its peripheral influences.

Advanced silk materials for musculoskeletal tissue regeneration.

Musculoskeletal diseases are the leading causes of chronic pain and physical disability, affecting millions of individuals worldwide. Over the past two decades, significant progress has been made in the field of bone and cartilage tissue engineering to combat the limitations of conventional treatments. Among various materials used in musculoskeletal tissue regeneration, silk biomaterials exhibit unique mechanical robustness, versatility, favorable biocompatibility, and tunable biodegradation rate. As silk is an easy-to-process biopolymer, silks have been reformed into various materials formats using advanced bio-fabrication technology for the design of cell niches. Silk proteins also offer active sites for chemical modifications to facilitate musculoskeletal system regeneration. With the emergence of genetic engineering techniques, silk proteins have been further optimized from the molecular level with other functional motifs to introduce new advantageous biological properties. In this review, we highlight the frontiers in engineering natural and recombinant silk biomaterials, as well as recent progress in the applications of these new silks in the field of bone and cartilage regeneration. The future potentials and challenges of silk biomaterials in musculoskeletal tissue engineering are also discussed. This review brings together perspectives from different fields and provides insight into improved musculoskeletal engineering.

Mechanisms and therapeutic prospects of mesenchymal stem cells-derived exosomes for tendinopathy.

Tendinopathy is a debilitating and crippling syndrome resulting from the degeneration of tendon tissue, leading to loss of mechanical properties and function, and eventual tendon rupture. Unfortunately, there is currently no treatment for tendinopathy that can prevent or delay its progression. Exosomes are small extracellular vesicles that transport bioactive substances produced by cells, such as proteins, lipids, mRNAs, non-coding RNAs, and DNA. They can generate by mesenchymal stem cells (MSCs) throughout the body and play a role in intercellular communication and regulation of homeostasis. Recent research suggests that MSCs-derived exosomes (MSCs-exos) may serve as useful therapeutic candidates for promoting tendon healing. This review focuses on the function and mechanisms of MSCs-exos in tendinopathy treatment and discusses their potential application for treating this condition.

Transcriptomes of Testes at Different Developmental Stages in the Opsariichthys bidens Predict Key Genes for Testis Development and Spermatogenesis.

Testis development is a complex process involving multiple genes, and the molecular mechanisms underlying testis development in Opsariichthys bidens remain unclear. We performed transcriptome sequencing analysis on a total of 12 samples of testes from stages II, III, IV, and V of O. bidens and obtained a total of 79.52 Gb clean data, as well as 288,573 transcripts and 116,215 unigenes. Differential expression analysis showed that 22,857 differentially expressed genes (DEGs) were screened in six comparison groups (III vs. II, IV vs. II, V vs. II, IV vs. III, V vs. III, and V vs. IV). Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs showed that six comparison groups were significantly enriched for a total of 20 significantly up- or down-regulated pathways, including six pathways related to signal transduction, three pathways related to energy metabolism, five pathways related to disease, and two pathways related to ribosomes. Furthermore, our investigation revealed that DEGs were enriched in several important functional pathways, such as Huntington's disease signaling pathway, TGF-ß signaling pathway, and ribosome signaling pathway. Protein-protein interaction network analysis of DEGs identified 63 up-regulated hub genes, including 9 kinesin genes and 2 cytoplasmic dynein genes, and 39 down-regulated hub genes, including 13 ribosomal protein genes. This result contributes to the knowledge of spermatogenesis and testis development in O. bidens.

Genome-wide characterization of the cytosolic sulfotransferase 1B member 1 (SULT1B1) family and its expression responses to sulfide stress in the razor clam Sinonovacula constricta.

The razor clam (Sinonovacula constricta), a typical burrowing organism in the intertidal zones, is often exposed to sulfide environment and shows strong sulfide tolerance. Located downstream of the sulfur metabolism pathway, cytosolic sulfotransferase family 1B member 1 (SULT1B1) is a key enzyme catalysing the sulfonation reaction, and plays an important role in the biotransformation of endogenous substances such as thyroid hormones (THs). To investigate their roles in sulfide resistance, a systematic analysis of S. constricta SULT1B1s (ScSULT1B1s), including genomic distribution, phylogenetic relationships, gene structure, conserved motifs, and expression profiles under sulfide stress, was performed. A total of 10 ScSULT1B1 genes were found in the S. constricta genome. Sequence analysis showed that ScSULT1B1 gene family encoded 155-425 amino acids, containing four catalytic active sites (K, N, H, and S), one PAPS binding domain at the N-terminus, and one PAPS binding and dimerization domain at the C-terminus. The spatial-temporal expression patterns of ScSULT1B1s were further estimated by quantitative real-time PCR (qRT-PCR). Among them, partial ScSULT1B1s showed significantly high expression in the gill, hepatopancreas, and siphon. Furthermore, the response expression of certain ScSULT1B1s significantly fluctuated under sulfide stress. Together, our results suggest that ScSULT1B1s, by mediating the sulfonation reaction, may regulate THs levels to maintain basic metabolic and immune functions, making S. constricta highly sulfide tolerant.

MSdb: An integrated expression atlas of human musculoskeletal system.

The global prevalence and burden of musculoskeletal (MSK) disorders are immense. Advancements in next-generation sequencing (NGS) have generated vast amounts of data, accelerating the research of pathological mechanisms and the development of therapeutic approaches for MSK disorders. However, scattered datasets across various repositories complicate uniform analysis and comparison. Here, we introduce MSdb, a database for visualization and integrated analysis of next-generation sequencing data from human musculoskeletal system, along with manually curated patient phenotype data. MSdb provides various types of analysis, including sample-level browsing of metadata information, gene/miRNA expression, and single-cell RNA-seq dataset. In addition, MSdb also allows integrated analysis for cross-samples and cross-omics analysis, including customized differentially expressed gene/microRNA analysis, microRNA-gene network, scRNA-seq cross-sample/disease integration, and gene regulatory network analysis. Overall, systematic categorizing, standardized processing, and freely accessible knowledge features MSdb a valuable resource for MSK research community.