Whole-Transcriptome Sequence of Degenerative Meniscus Cells Unveiling Diagnostic Markers and Therapeutic Targets for Osteoarthritis

Meniscus plays an important role in joint homeostasis. Tear or degeneration of meniscus might facilitate the process of knee osteoarthritis (OA). Hence, to investigate the transcriptome change during meniscus degeneration, we reveal the alterations of messenger RNA (mRNA), microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA) in meniscus during OA by whole-transcriptome sequence. A total of 375 mRNAs, 15 miRNAs, 56 lncRNAs, and 90 circRNAs were significantly altered in the degenerative meniscus treated with interleukin-1β (IL-1β). More importantly, highly specific co-expression RNA (ceRNA) networks regulated by lncRNA LOC107986251-miR-212-5p-SESN3 and hsa_circ_0018069-miR-147b-3p-TJP2 were screened out during IL-induced meniscus degeneration, unveiling potential therapeutic targets for meniscus degeneration during the OA process. Furthermore, lipocalin-2 (LCN2) and RAB27B were identified as potential biomarkers in meniscus degeneration by overlapping three previously constructed databases of OA menisci. LCN2 and RAB27B were both upregulated in osteoarthritic menisci and IL-1β-treated menisci and were highly associated with the severity of OA. This could introduce potential novel molecules into the database of clinical diagnostic biomarkers and possible therapeutic targets for early-stage OA treatment.

Identification and validation of pivotal genes related to age-related meniscus degeneration based on gene expression profiling analysis and in vivo and in vitro models detection

Background The componential and structural change in the meniscus with aging would increase the tissue vulnerability of the meniscus, which would induce meniscus tearing. Here, we investigated the molecular mechanism of age-related meniscus degeneration with gene expression profiling analysis, and validate pivotal genes in vivo and in vitro models. Methods The GSE45233 dataset, including 6 elderly meniscus samples and 6 younger meniscus samples, was downloaded from the Gene Expression Omnibus (GEO) database. To screen the differential expression of mRNAs and identify the miRNAs targeting hub genes, we completed a series of bioinformatics analyses, including functional and pathway enrichment, protein–protein interaction network, hub genes screening, and construction of a lncRNA–miRNA–mRNA network. Furthermore, crucial genes were examined in human senescent menisci, mouse senescent meniscus tissues and mouse meniscus cells stimulated by IL-1β. Results In total, the most significant 4 hub genes (RRM2, AURKB, CDK1, and TIMP1) and 5 miRNAs (hsa-miR-6810-5p, hsa-miR-4676-5p, hsa-miR-6877-5p, hsa-miR-8085, and hsa-miR-6133) that regulated such 4 hub genes, were finally identified. Moreover, these hub genes were decreased in meniscus cells in vitro and meniscus tissues in vivo, which indicated that hub genes were related to meniscus senescence and could serve as potential biomarkers for age-related meniscus tearing. Conclusions In short, the integrated analysis of gene expression profile, co-expression network, and models detection identified pivotal genes, which elucidated the possible molecular basis underlying the senescence meniscus and also provided prognosis clues for early-onset age-related meniscus tearing.

Identification And Validation of Pivotal Genes Related To Meniscus Senescence Based On Gene Expression Profiling Analysis And In Vivo And In Vitro Models Detection

Background: The compositional change in the meniscus with aging would increase the tissue vulnerability of the meniscus, which would induce meniscus tearing. Here, we investigated the molecular mechanism of age-related meniscus degeneration with gene expression profiling analysis, and validate pivotal genes in vivo and in vitro models.Methods: The GSE45233 dataset, including 6 elderly meniscus samples and 6 younger meniscus samples, was downloaded from the Gene Expression Omnibus (GEO) database. To screen the differential expression of mRNAs, identify the miRNAs targeting hub genes, and forecast the potentially toxic drugs, we completed a series of bioinformatics analyses, including functional and pathway enrichment, protein-protein interaction network, hub genes screening, construction of a lncRNA–miRNA–mRNA network, and molecular docking of potential drugs. Furthermore, crucial genes were examined in human senescent menisci, mouse senescent meniscus tissues and mouse meniscus cells stimulated by IL-1β.Results: In total, the most significant 4 hub genes (RRM2, AURKB, CDK1, and TIMP1), 5 miRNAs (hsa-miR-6810-5p, hsa-miR-4676-5p, hsa-miR-6877-5p, hsa-miR-8085, and hsa-miR-6133) that regulated such 4 hub genes, and potential toxic drugs (Cladribine, Danusertib, Barasertib, Riviciclib, and Dinaciclib) that had a targeting effect on these genes, were finally identified. Moreover, these hub genes were decreased in meniscus cells in vitro and meniscus tissues in vivo, which indicated that hub genes were related to meniscus senescence and could serve as potential biomarkers for age-related meniscus tearing.Conclusions: In short, the integrated analysis of gene expression profile, co-expression network, and models detection identified pivotal genes, which elucidated the possible molecular basis underlying the senescence meniscus and also provided prognosis clues for early-onset age-related meniscus tearing.

Identification and Validation of Hub Genes Related to Meniscus Senescence Based on Gene Expression Profiling Analysis

Background: The incidence of meniscal injury is on the rise, partly due to the general aging of the population. The compositional change in the meniscus with aging would increase the tissue vulnerability of the meniscus, which would induce meniscus tearing. Here, we investigated the molecular mechanism of age-related meniscus degeneration with gene expression profiling analysis.Methods: The GSE45233 dataset, including 6 elderly meniscus samples and 6 younger meniscus samples, which were obtained from patients undergoing arthroscopic partial meniscectomy, was downloaded from the Gene Expression Omnibus (GEO) database for subsequent bioinformatics analysis. To screen the differential expression of mRNAs, identify the miRNAs targeting hub genes, and forecast the potentially toxic drugs, we completed a series of bioinformatics analyses, including functional and pathway enrichment analysis, protein-protein interaction network, hub genes screening, construction of a lncRNA–miRNA–mRNA network, and molecular docking of potential drugs. Furthermore, hub genes were examined in human senescent menisci, mouse senescent meniscus tissues and mouse meniscus cells stimulated by IL-1β.Results: In total, the most significant 4 hub genes (RRM2, AURKB, CDK1, and TIMP1), 5 miRNAs (hsa-miR-6810-5p, hsa-miR-4676-5p, hsa-miR-6877-5p, hsa-miR-8085, and hsa-miR-6133) that could regulate such 4 hub genes and potential toxic drugs (Cladribine, Danusertib, Barasertib, Riviciclib, and Dinaciclib) that may have a targeting effect on these genes, were finally identified. The functional enrichment results showed that hub genes were mainly concentrated in aging and regulation of the cell cycle process. Further pathways enrichment analysis of these miRNA revealed that these miRNAs were involved in the synthesis of glycosaminoglycans. The hub genes were decreased in meniscus cells in vitro and meniscus tissues in vivo, which indicated that hub genes were related to meniscus senescence.Conclusions: In a word, our current study would provide a basis for finding markers of the aging meniscus to a certain extent.

Autologous meniscus fragments embedded in atelocollagen gel enhance meniscus repair in a rabbit model

Aims Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect. Methods A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus. Results In vitro immunohistochemistry revealed that the meniscus cells migrated from the minced meniscus and proliferated in the gel. Furthermore, histological analysis suggested that the minced meniscus embedded in the atelocollagen gel produced tissue resembling the native meniscus in vivo. The minced meniscus group also had a higher Pauli’s score compared to the defect and atelocollagen groups. Conclusion Our data show that cells in minced meniscus can proliferate, and that implantation of the minced meniscus within atelocollagen induces meniscus regeneration, thus suggesting a novel therapeutic alternative for meniscus tears. Cite this article: Bone Joint Res 2021;10(4):269–276.

Osteomielite crônica mandibular em pacientes pediátricos

A osteomielite é considerada uma doença incomum em pacientes saudáveis e de difícil diagnóstico e tratamento. Estudos sugerem que patologias infecciosas periodontais e peri-implantares como gengivites, periodontites e peri-implantites atuam como fatores mais comuns, predisponentes para osteomielites dos maxilares. Osteomielites crônicas exigem tratamento com cobertura antibiótica e procedimentos cirúrgicos. O tratamento envolve avaliação, determinação da etiologia, terapia antimicrobiana, desbridamento da lesão, remoção dos sequestros ósseos e decorticação óssea associada ao emprego sistêmico de antimicrobianos, geralmente de amplo espectro. O presente trabalho tem como objetivo relatar dois casos clínicos de osteomielite crônica infantil, bem como realizar uma análise comparativa de casos clínicos já publicados em artigos científicos. Pôde-se concluir que a associação de características clínicas, exames histopatológicos e achados radiográficos podem reunir características comuns para diversos tipos de osteomielite. Portanto, devem culminar em fatores contribuintes para o diagnóstico final. Em ambos os casos relatados, o tratamento foi eficaz utilizando terapia medicamentosa com o uso de anti-inflamatórios e antibióticos aliados a tratamento cirúrgico que consistiu em desbridamento da lesão. Ambos os pacientes foram acompanhados e proservados, não havendo recidiva. Descritores: Osteomielite; Antibacterianos; Patologia Bucal; Procedimentos Cirúrgicos Bucais.ReferênciasHupp JR, Ellis E, Tucker MR. Cirurgia oral e maxilofacial contemporânea. Rio de Janeiro: Elsevier; 2011.Lew DP, Waldvogel FA. Osteomyelitis. Lancet. 2004;364(9431):369-79.Baltieri BR, Gabrielli MAC, Gabrielli MFR, Pereira Filho VA, Lopes FS, Leite VA. Osteomielite em mandíbula de criança. Rev Odontol Unesp. 2014;43(N Especial):262.Gaetti Júnior E, Gaetti Jardim EC, Faverani LP, Landucci KC, Landucci LF. Osteomielite crônica dos maxilares: aspectos clínicos, terapêuticos e microbiológicos. Salusvita. 2008;27(1):125-39.Carek PJ, Dickerson LM, Sack JL . Diagnosis and management of osteomyelitis. Am Fam Physician. 2001;63(12):2413-20.6. Miloro M, Ghali GE, Larse PE, Waite PD. Princípios de cirurgia bucomaxilofacial de Peterson. 2ed. São Paulo: Santos; 2008.Neville BW, Damm DD, Allen CM, Bouquot JE. Patologia oral e maxilofacial. Rio de Janeiro: Elsevier; 2011.Watanabe T, Ono H, Morimoto Y, Otsuki Y, Shirai M, Endoh A et al. Skull involvement in a pediatric case of chronic recurrent multifocal osteomyelitis. Nagoya J Med Sci. 2015;77(3):493-500.Suei Y, Taguchi A, Tanimoto K. Diagnosis and classification of mandibular osteomyelitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(2):207-14.Masocatto DC, Oliveira MM, Mendonça JCG. Osteomielite crônica mandibular: relato de caso. Arch Health Invest.2017;6(2):48-52Ferraria N, Marques JG, Ramos F, Lopes G, Fonseca JG, Neves MC. Osteomielite crónica multifocal recorrente: série de 4 casos clínicos tratados com bifosfonatos. Acta Reumatol Port. 2014;39(1):38-45Paim LB, Liphaus BL, Rocha AC, Castellanos LZA, Silva CAA. Osteomielite crônica multifocal recorrente da mandíbula: relato de três casos. J Pediatr. 2003;79(5):467-70.Sousa MV, Malheiro R, Neves J, Varandas L, Conde M. Osteomielite crónica não bacteriana unifocal da mandíbula. Acta Reumatol Port. 2014:39;94-95Kadom N, Egloff A, Obeid G, Bandarkar A, Vezina G. Juvenile mandibular chronic osteomyelitis: multimodality imaging findings. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111(3):e38-43.Theologie-Lygidakis N, Schoinohoriti O, Iatrou I. Surgical management of primary chronic osteomyelitis of the jaws in children: a prospective analysis of five cases and review of the literature. Oral Maxillofac Surg. 2011;15(1):41-50.Wang L, Wu Y, Tan Y, Fei X, Deng Y, Cao H et al. Cytotoxic effects of the quinolone levofloxacin on rabbit meniscus cells. J Appl Toxicol. 2014;34(8):870-77.Deng Y, Chen B, Qi Y, Magdalou J, Wang H, Chen L. The effects of levofloxacin on rabbit anterior cruciate ligament cells in vitro. Toxicol Appl Pharmacol. 2011;257(1):67-73.Obel G, Krogdahl A, Thygesen T, Godballe C. Juvenile mandibular chronic osteomyelitis: 3 cases and a literature review. J Oral Maxillofac Surg. 2013;71(2):305-9.