المؤلفون: Abdalla, Amira, Benissan-Messan, Dathe, Chen, Yupeng, Grassie, Kevin, Han, Biao, Han, Lin, Jayasuriya, Chathuraka T., Ji, Jenny, Khan, Yusuf, Kilian, Emily, Korcari, Antonion, Kwok, Bryan, Lin, Xiao, Liu, Huinan, Loiselle, Alayna E., Nichols, Anne E.C., O’Neil, Meghan, Payne, Emma, Quint, Jacob, Samandari, Mohamadmahdi, Sapowadia, Avin, Seo, Catherine, Shen, Jie, Tamayol, Ali, Trivedi, Jay, Wang, Chao, Wu, Kang, Xiao, Ding, Xu, Pengcheng, Yang, Lei, Yau, Anne, Yeh, Kaitlyn, Yin, Jiewei, Zhang, Chaoxing, Zhang, Wuxia, Zhou, Libo, Zhu, Hua

المصدر: Musculoskeletal Tissue Engineering ; page xi-xiii

الإتاحة: https://doi.org/10.1016/b978-0-12-823893-6.00016-4Test
https://api.elsevier.com/content/article/PII:B9780128238936000164?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:B9780128238936000164?httpAccept=text/plainTest

المؤلفون: Yang, Daniel S., Trivedi, Jay, Betensky, Daniel, Desai, Salomi, Owens, Brett D., Jayasuriya, Chathuraka T.

المصدر: Current Stem Cell Research & Therapy ; volume 19 ; ISSN 1574-888X

الوصف: Introduction: Kartogenin (KGN) is a synthetic small molecule that stimulates chondrogenic cellular differentiation by activating smad-4/5 pathways. KGN has been proposed as a feasible alternative to expensive biologic growth factors, such as transforming growth factor β, which remain under strict regulatory scrutiny when it comes to use in patients. Method: This study reports the previously unexplored effects of KGN stimulation on cartilage- derived mesenchymal progenitor cells (CPCs), which have been shown to be effective in applications of cell-based musculoskeletal tissue regeneration. Our findings demonstrate that KGN treatment significantly increased markers of chondrogenesis, SOX9 and COL2 following 3-10 days of treatment in human CPCs. Result: KGN treatment also resulted in a significant dose-dependent increase in GAG production in CPCs. The same efficacy was not observed in human marrow-derived stromal cells (BM-MSCs); however, KGN significantly reduced mRNA expression of cell hypertrophy markers, COL10 and MMP13, in BM-MSCs. Parallel to these mRNA expression results, KGN led to a significant decrease in protein levels of MMP-13 both at 0-5 days and 5-10 days following KGN treatment. Conclusion: In conclusion, this study demonstrates that KGN can boost the chondrogenicity of CPCs and inhibit hypertrophic terminal differentiation of BM-MSCs.

الإتاحة: https://doi.org/10.2174/011574888x314971240511151616Test

المؤلفون: Desai, Salomi, Dooner, Mark, Newberry, Jake, Twomey-Kozak, John, Molino, Janine, Trivedi, Jay, Patel, Jay M., Owens, Brett D., Jayasuriya, Chathuraka T.

المساهمون: Orthopaedic Research and Education Foundation, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, U.S. Department of Defense

المصدر: Frontiers in Bioengineering and Biotechnology ; volume 10 ; ISSN 2296-4185

الوصف: Meniscal tearing in the knee increases the risk of post-traumatic osteoarthritis (OA) in patients. The therapeutic application of tissue-specific mesenchymal progenitor cells is currently being investigated as an emerging biologic strategy to help improve healing of musculoskeletal tissues like meniscal fibrocartilage and articular hyaline cartilage. However, many of these approaches involve isolating cells from healthy tissues, and the low yield of rare progenitor populations (< 1% of total cells residing in tissues) can make finding a readily available cell source for therapeutic use a significant logistical challenge. In the present study, we investigated the therapeutic efficacy of using expanded cartilage-derived and bone marrow-derived progenitor cell lines, which were stabilized using retroviral SV40, for repair of meniscus injury in a rodent model. Our findings indicate that these cell lines express the same cell surface marker phenotype of primary cells (CD54+, CD90+, CD105+, CD166+), and that they exhibit improved proliferative capacity that is suitable for extensive expansion. Skeletally mature male athymic rats treated with 3.2 million cartilage-derived progenitor cell line exhibited approximately 79% greater meniscal tear reintegration/healing, compared to injured animals that left untreated, and 76% greater compared to animals treated with the same number of marrow-derived stromal cells. Histological analysis of articular surfaces also showed that cartilage-derived progenitor cell line treated animals exhibited reduced post-traumatic OA associated articular cartilage degeneration. Stable cell line treatment did not cause tumor formation or off-target engraftment in animals. Taken together, we present a proof-of-concept study demonstrating, for the first time, that intra-articular injection of a stable human cartilage-derived progenitor cell line stimulates meniscus tear healing and provide chondroprotection in an animal model. These outcomes suggest that the use of stable cell lines may help ...

الإتاحة: https://doi.org/10.3389/fbioe.2022.970235Test

المؤلفون: McNamara, Jeffrey T., Huntington, Kelsey E., Borys, Samantha, Jayasuriya, Chathuraka T., Brossay, Laurent

المساهمون: National Institute of Allergy and Infectious Diseases

المصدر: Scientific Reports ; volume 11, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: Due to redundancy with other tyrosine phosphatases, the ubiquitously expressed tyrosine phosphatase SHP-2 (encoded by Ptpn11 ) is not required for T cell development. However, Ptpn11 gene deletion driven by CD4 Cre recombinase leads to cartilage tumors in the wrist. Using a fate mapping system, we demonstrate that wrist tumor development correlates with increased frequency and numbers of non-hematopoietic lineage negative CD45 negative cells with a bone chondrocyte stromal cell precursor cell (BCSP) phenotype. Importantly, the BCSP subset has a history of CD4 expression and a marked wrist location tropism, explaining why the wrist is the main site of tumor development. Mechanistically, we found that in SHP-2 absence, SOX-9 is no longer regulated, leading to an uncontrolled proliferation of the BCSP subset. Altogether, these results identify a unique subset of chondrocyte precursors tightly regulated by SHP-2. These findings underscore the need for the development of methods to therapeutically target this subset of cells, which could potentially have an impact on treatment of SHP-2 dysfunction linked debilitating diseases.

الإتاحة: https://doi.org/10.1038/s41598-021-99339-0Test
https://www.nature.com/articles/s41598-021-99339-0.pdfTest
https://www.nature.com/articles/s41598-021-99339-0Test

المؤلفون: Trivedi, Jay, Betensky, Daniel, Desai, Salomi, Jayasuriya, Chathuraka T.

المساهمون: National Institute of Arthritis and Musculoskeletal and Skin Diseases, U.S. Department of Defense

المصدر: Frontiers in Bioengineering and Biotechnology ; volume 9 ; ISSN 2296-4185

مصطلحات موضوعية: Biomedical Engineering, Histology, Bioengineering, Biotechnology

الوصف: Surgical repair of meniscus injury is intended to help alleviate pain, prevent further exacerbation of the injury, restore normal knee function, and inhibit the accelerated development of post-traumatic osteoarthritis (PTOA). Meniscus injuries that are treated poorly or left untreated are reported to significantly increase the risk of PTOA in patients. Current surgical approaches for the treatment of meniscus injuries do not eliminate the risk of accelerated PTOA development. Through recent efforts by scientists to develop innovative and more effective meniscus repair strategies, the use of biologics, allografts, and scaffolds have come into the forefront in pre-clinical investigations. However, gauging the extent to which these (and other) approaches inhibit the development of PTOA in the knee joint is often overlooked, yet an important consideration for determining the overall efficacy of potential treatments. In this review, we catalog recent advancements in pre-clinical therapies for meniscus injuries and discuss the assessment methodologies that are used for gauging the success of these treatments based on their effect on PTOA severity. Methodologies include histopathological evaluation of cartilage, radiographic evaluation of the knee, analysis of knee function, and quantification of OA predictive biomarkers. Lastly, we analyze the prevalence of these methodologies using a systemic PubMed ® search for original scientific journal articles published in the last 3-years. We indexed 37 meniscus repair/replacement studies conducted in live animal models. Overall, our findings show that approximately 75% of these studies have performed at least one assessment for PTOA following meniscus injury repair. Out of this, 84% studies have reported an improvement in PTOA resulting from treatment.

الإتاحة: https://doi.org/10.3389/fbioe.2021.787330Test

المؤلفون: Liu, Wenguang, Brodsky, Alexander S., Feng, Meng, Liu, Yajun, Ding, Jing, Jayasuriya, Chathuraka T., Chen, Qian

المساهمون: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of General Medical Sciences, China Scholarship Council

المصدر: Frontiers in Cell and Developmental Biology ; volume 9 ; ISSN 2296-634X

مصطلحات موضوعية: Cell Biology, Developmental Biology

الوصف: Human osteoarthritic cartilage contains not only chondrocytes (OACs), but also mesenchymal stromal cells (OA-MSCs), whose abundance increases during osteoarthritis (OA). However, it is not clear how OA-MSC contributes to OA pathogenesis. Here, we show that aging OA-MSC plays an important role in cell senescence, fibrosis, and inflammation in cartilage. Protein array analysis indicates that OA-MSC expresses pro-inflammatory senescence associated secretory phenotype (SASP) including IL-1β, IL-6, IL-8, and CXCL1, 5, and 6, which play key roles in OA pathogenesis. OAC is a main recipient of the inflammatory signals by expressing receptors of cytokines. RNAseq analysis indicates that the transition from normal cartilage stromal cells (NCSCs) to OA-MSC during aging results in activation of SASP gene expression. This cell transition process can be recapitulated by a serial passage of primary OAC in cell culture comprising (1) OAC dedifferentiation into NCSC-like cells, and (2) its subsequent senescence into pro-inflammatory OA-MSC. While OAC dedifferentiation is mediated by transcriptional repression of chondrogenic gene expression, OA-MSC senescence is mediated by transcriptional activation of SASP gene expression. We postulate that, through replication-driven OAC dedifferentiation and mesenchymal stromal cell (MSC) senescence, OA-MSC becomes an internal source of sterile inflammation in human cartilage joint.

الإتاحة: https://doi.org/10.3389/fcell.2021.725071Test

مستخلص: Methods for reducing the severity of an arthritic condition or repairing an osteochondral defect are carried out by administering to a subject compositions comprising a member of the matrilin family of proteins, e.g., a matrilin protein, fragment thereof, or nucleic acid encoding the protein or fragment.

المؤلفون: Hu, Nan, Gao, Yun, Jayasuriya, Chathuraka T., Liu, Wenguang, Du, Heng, Ding, Jing, Feng, Meng, Chen, Qian

المساهمون: National Institutes of Health

المصدر: Arthritis Research & Therapy ; volume 21, issue 1 ; ISSN 1478-6362

الإتاحة: https://doi.org/10.1186/s13075-019-1949-0Test

المؤلفون: Hodax, Juanita K., Quintos, Jose Bernardo, Gruppuso, Philip A., Chen, Qian, Desai, Salomi, Jayasuriya, Chathuraka T.

المساهمون: van Wijnen, Andre

المصدر: PLOS ONE ; volume 14, issue 6, page e0218399 ; ISSN 1932-6203

الإتاحة: https://doi.org/10.1371/journal.pone.0218399Test

المؤلفون: Shigley, Christian, Trivedi, Jay, Meghani, Ozair, Owens, Brett D., Jayasuriya, Chathuraka T.

المصدر: Bioengineering (Basel); Jun2023, Vol. 10 Issue 6, p741, 17p

مصطلحات موضوعية: ENDOCHONDRAL ossification, CARTILAGE, ARTICULAR cartilage, HYPERTROPHY, SOFT tissue injuries, OSTEOARTHRITIS

مستخلص: Current clinical strategies for restoring cartilage defects do not adequately consider taking the necessary steps to prevent the formation of hypertrophic tissue at injury sites. Chondrocyte hypertrophy inevitably causes both macroscopic and microscopic level changes in cartilage, resulting in adverse long-term outcomes following attempted restoration. Repairing/restoring articular cartilage while minimizing the risk of hypertrophic neo tissue formation represents an unmet clinical challenge. Previous investigations have extensively identified and characterized the biological mechanisms that regulate cartilage hypertrophy with preclinical studies now beginning to leverage this knowledge to help build better cartilage. In this comprehensive article, we will provide a summary of these biological mechanisms and systematically review the most cutting-edge strategies for circumventing this pathological hallmark of osteoarthritis. [ABSTRACT FROM AUTHOR]

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