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Article ; Online: MMP13-Overexpressing Mesenchymal Stem Cells Enhance Bone Tissue Formation in the Presence of Collagen Hydrogel.

Arai, Yoshie / Lee, Soo-Hong

Tissue engineering and regenerative medicine

2023 Volume 20, Issue 3, Page(s) 461–471

Abstract: Background: Matrix metalloproteinases (MMPs) are proteins involved in the repair and remodeling the extracellular matrix (ECM). MMP13 is essential for bone development and healing through the remodeling of type I collagen (COL1), the main component of ... ...

Abstract	Background: Matrix metalloproteinases (MMPs) are proteins involved in the repair and remodeling the extracellular matrix (ECM). MMP13 is essential for bone development and healing through the remodeling of type I collagen (COL1), the main component of the ECM in bone tissue. Mesenchymal stem cells (MSCs)-based cell therapy has been considered a promising approach for bone regeneration because of their osteogenic properties. However, the approaches using MSC to completely regenerate bone tissue have been limited. To overcome the limitation, genetic engineering of MSC could be a strategy for promoting regeneration efficacy. Methods: We performed in vitro and in vivo experiments using MMP13-overexpressing MSCs in the presence of COL1. To examine MMP13-overexpressing MSCs in vivo, we prepared a fibrin/COL1-based hydrogel to encapsulate MSCs and subcutaneously implanted gel-encapsulated MSCs in nude mice. We found that the osteogenic marker genes, ALP and RUNX2, were upregulated in MMP13-overexpressing MSCs through p38 phosphorylation. In addition, MMP13 overexpression in MSCs stimulated the expression of integrin α3, which is up-stream receptor of p38, and substantially increased osteogenic differentiation potential of MSCs. Bone tissue formation in MMP13-overexpressing MSCs was significantly higher than that in control MSCs. Taken together, our findings demonstrate that MMP13 is not only an essential factor for bone development and bone healing but also has a pivotal role in promoting osteogenic differentiation of MSCs to induce bone formation. Conclusion: MSCs Genetically engineered to overexpress MMP13, which have a powerful potential to differentiate into the osteogenic cells, might be beneficial in bone disease therapy.
MeSH term(s)	Mice ; Animals ; Osteogenesis ; Hydrogels ; Mice, Nude ; Matrix Metalloproteinase 13/genetics ; Bone and Bones ; Mesenchymal Stem Cells/metabolism ; Collagen/metabolism
Chemical Substances	Hydrogels ; Matrix Metalloproteinase 13 (EC 3.4.24.-) ; Collagen (9007-34-5)
Language	English
Publishing date	2023-04-11
Publishing country	Korea (South)
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2677535-9
ISSN	2212-5469 ; 1738-2696
ISSN (online)	2212-5469
ISSN	1738-2696
DOI	10.1007/s13770-023-00535-y
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Article: Emerging nano-scale delivery systems for the treatment of osteoporosis.

Dayanandan, Anoop Puthiyoth / Cho, Woong Jin / Kang, Hyemin / Bello, Alvin Bacero / Kim, Byoung Ju / Arai, Yoshie / Lee, Soo-Hong

Biomaterials research

2023 Volume 27, Issue 1, Page(s) 68

Abstract: Osteoporosis is a pathological condition characterized by an accelerated bone resorption rate, resulting in decreased bone density and increased susceptibility to fractures, particularly among the elderly population. While conventional treatments for ... ...

Abstract	Osteoporosis is a pathological condition characterized by an accelerated bone resorption rate, resulting in decreased bone density and increased susceptibility to fractures, particularly among the elderly population. While conventional treatments for osteoporosis have shown efficacy, they are associated with certain limitations, including limited drug bioavailability, non-specific administration, and the occurrence of adverse effects. In recent years, nanoparticle-based drug delivery systems have emerged as a promising approach for managing osteoporosis. Nanoparticles possess unique physicochemical properties, such as a small size, large surface area-to-volume ratio, and tunable surface characteristics, which enable them to overcome the limitations of conventional therapies. These nanoparticles offer several advantages, including enhanced drug stability, controlled release kinetics, targeted bone tissue delivery, and improved drug bioavailability. This comprehensive review aims to provide insights into the recent advancements in nanoparticle-based therapy for osteoporosis. It elucidates the various types of nanoparticles employed in this context, including silica, polymeric, solid lipid, and metallic nanoparticles, along with their specific processing techniques and inherent properties that render them suitable as potential drug carriers for osteoporosis treatment. Furthermore, this review discusses the challenges and future suggestions associated with the development and translation of nanoparticle drug delivery systems for clinical use. These challenges encompass issues such as scalability, safety assessment, and regulatory considerations. However, despite these challenges, the utilization of nanoparticle-based drug delivery systems holds immense promise in revolutionizing the field of osteoporosis management by enabling more effective and targeted therapies, ultimately leading to improved patient outcomes.
Language	English
Publishing date	2023-07-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2775188-0
ISSN	2055-7124 ; 1226-4601
ISSN (online)	2055-7124
ISSN	1226-4601
DOI	10.1186/s40824-023-00413-7
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Article: Progress and emerging techniques for biomaterial-based derivation of mesenchymal stem cells (MSCs) from pluripotent stem cells (PSCs).

Prakash, Nityanand / Kim, Jiseong / Jeon, Jieun / Kim, Siyeon / Arai, Yoshie / Bello, Alvin Bacero / Park, Hansoo / Lee, Soo-Hong

Biomaterials research

2023 Volume 27, Issue 1, Page(s) 31

Abstract: The use of mesenchymal stem cells (MSCs) for clinical purposes has skyrocketed in the past decade. Their multilineage differentiation potentials and immunomodulatory properties have facilitated the discovery of therapies for various illnesses. MSCs can ... ...

Abstract	The use of mesenchymal stem cells (MSCs) for clinical purposes has skyrocketed in the past decade. Their multilineage differentiation potentials and immunomodulatory properties have facilitated the discovery of therapies for various illnesses. MSCs can be isolated from infant and adult tissue sources, which means they are easily available. However, this raises concerns because of the heterogeneity among the various MSC sources, which limits their effective use. Variabilities arise from donor- and tissue-specific differences, such as age, sex, and tissue source. Moreover, adult-sourced MSCs have limited proliferation potentials, which hinders their long-term therapeutic efficacy. These limitations of adult MSCs have prompted researchers to develop a new method for generating MSCs. Pluripotent stem cells (PSCs), such as embryonic stem cells and induced PSCs (iPSCs), can differentiate into various types of cells. Herein, a thorough review of the characteristics, functions, and clinical importance of MSCs is presented. The existing sources of MSCs, including adult- and infant-based sources, are compared. The most recent techniques for deriving MSCs from iPSCs, with a focus on biomaterial-assisted methods in both two- and three-dimensional culture systems, are listed and elaborated. Finally, several opportunities to develop improved methods for efficiently producing MSCs with the aim of advancing their various clinical applications are described.
Language	English
Publishing date	2023-04-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2775188-0
ISSN	2055-7124 ; 1226-4601
ISSN (online)	2055-7124
ISSN	1226-4601
DOI	10.1186/s40824-023-00371-0
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Article: Therapeutic potential of epiphyseal growth plate cells for bone regeneration in an osteoporosis model.

Baek, Inho / Bello, Alvin Bacero / Jeon, Jieun / Arai, Yoshie / Cha, Byung-Hyun / Kim, Byoung Ju / Lee, Soo-Hong

Journal of tissue engineering

2022 Volume 13, Page(s) 20417314221116754

Abstract: Bone growth occurs in the epiphyseal growth plate (EGP) and epiphyseal growth plate cells (EGPCs) exist in EGP. EGPCs, including skeletal stem cells (SSCs), are cells that induce bone growth and development through endochondral ossification. Recently, ... ...

Abstract	Bone growth occurs in the epiphyseal growth plate (EGP) and epiphyseal growth plate cells (EGPCs) exist in EGP. EGPCs, including skeletal stem cells (SSCs), are cells that induce bone growth and development through endochondral ossification. Recently, the superiority of bone regeneration through endochondral ossification has been reported. Our study compared EGPCs with bone marrow-derived mesenchymal stem cells (BM-MSCs) and suggested the therapeutic potential of new bone regeneration. In this study, we analyzed the characteristics between EGPCs and BM-MSCs based on morphological characteristics and molecular profiles. EGPCs expressed chondrogenic and osteogenic markers higher than BM-MSCs. Additionally, in co-culture with BM-MSCs, EGPCs induced an increase in chondrogenic, osteogenic, and hypertrophic markers of BM-MSCs. Finally, EGPCs induced higher bone regeneration than BM-MSCs in the osteoporosis model. Overall, we suggest the possibility of EGPCs as cell therapy for effective bone regeneration.
Language	English
Publishing date	2022-08-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2573915-3
ISSN	2041-7314
ISSN	2041-7314
DOI	10.1177/20417314221116754
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Article ; Online: Combinatorial Effect of Mesenchymal Stem Cells and Extracellular Vesicles in a Hydrogel on Cartilage Regeneration.

Cho, Woong Jin / Ahn, Jinsung / Lee, Minju / Choi, Hyejong / Park, Sunghyun / Cha, Kyung-Yup / Lee, SunJun / Arai, Yoshie / Lee, Soo-Hong

Tissue engineering and regenerative medicine

2022 Volume 20, Issue 1, Page(s) 143–154

Abstract: Background: Mesenchymal stem cells (MSCs) are used for tissue regeneration due to their wide differentiation capacity and anti-inflammatory effects. Extracellular vesicles (EVs) derived from MSCs are also known for their regenerative effects as they ... ...

Abstract	Background: Mesenchymal stem cells (MSCs) are used for tissue regeneration due to their wide differentiation capacity and anti-inflammatory effects. Extracellular vesicles (EVs) derived from MSCs are also known for their regenerative effects as they contain nucleic acids, proteins, lipids, and cytokines similar to those of parental cells. There are several studies on the use of MSCs or EVs for tissue regeneration. However, the combinatorial effect of human MSCs (hMSCs) and EVs is not clear. In this study, we investigated the combinatorial effect of hMSCs and EVs on cartilage regeneration via co-encapsulation in a hyaluronic-acid (HA)-based hydrogel. Methods: A methacrylic-acid-based HA hydrogel was prepared to encapsulate hMSCs and EVs in hydrogels. Through in vitro and in vivo analyses, we investigated the chondrogenic potential of the HA hydrogel-encapsulated with hMSCs and EVs. Results: Co-encapsulation of hMSCs with EVs in the HA hydrogel increased the chondrogenic differentiation of hMSCs and regeneration of damaged cartilage tissue compared with that of the HA hydrogel loaded with hMSCs only. Conclusion: Co-encapsulation of hMSCs and EVs in the HA hydrogel effectively enhances cartilage tissue regeneration due to the combinatorial therapeutic effect of hMSCs and EVs. Thus, in addition to cartilage tissue regeneration for the treatment of osteoarthritis, this approach would be a useful strategy to improve other types of tissue regeneration.
MeSH term(s)	Humans ; Hydrogels/pharmacology ; Cartilage/metabolism ; Hyaluronic Acid/pharmacology ; Mesenchymal Stem Cells/metabolism ; Extracellular Vesicles/metabolism
Chemical Substances	Hydrogels ; Hyaluronic Acid (9004-61-9)
Language	English
Publishing date	2022-12-08
Publishing country	Korea (South)
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2677535-9
ISSN	2212-5469 ; 1738-2696
ISSN (online)	2212-5469
ISSN	1738-2696
DOI	10.1007/s13770-022-00509-6
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Article ; Online: Generation of bioactive MSC-EVs for bone tissue regeneration by tauroursodeoxycholic acid treatment.

Cha, Kyung-Yup / Cho, Woongjin / Park, Sunghyun / Ahn, Jinsung / Park, Hyoeun / Baek, Inho / Lee, Minju / Lee, Sunjun / Arai, Yoshie / Lee, Soo-Hong

Journal of controlled release : official journal of the Controlled Release Society

2023 Volume 354, Page(s) 45–56

Abstract: Extracellular vesicles (EVs) are nano-sized carriers that reflect the parent cell's information and are known to mediate cell-cell communication. In order to overcome the disadvantages of mesenchymal stem cells (MSCs) in cell therapy, such as unexpected ... ...

Abstract	Extracellular vesicles (EVs) are nano-sized carriers that reflect the parent cell's information and are known to mediate cell-cell communication. In order to overcome the disadvantages of mesenchymal stem cells (MSCs) in cell therapy, such as unexpected differentiation leading to tumorization, immune rejection, and other side effects, EVs derived from MSCs (MSC-EVs) with the tissue regenerative function have been studied as new cell-free therapeutics. However, therapeutic applications of EVs require overcoming several challenges. First, the production efficiency of MSC-EVs should be increased at least as much as the quantity of them are required to their clinical application; second, MSC-EVs needs to show various functionality further, thereby increasing tissue regeneration efficiency. In this study, we treated tauroursodeoxycholic acid (TUDCA), a biological derivative known to regulate cholesterol, to MSCs and investigated whether TUDCA treatment would be able to increase EV production efficiency and tissue regenerative capacity of EVs. Indeed, it appears that TUDCA priming to MSC increases the yield of MSC-EVs >2 times by reducing the cellular cholesterol level in MSCs and increasing the exocytosis-related CAV1 expression. Interestingly, it was found that the EVs derived from TUDCA-primed MSCs (T-EV) contained higher amounts of anti-inflammatory cytokines (IL1RN, IL6, IL10, and IL11) and osteogenic proteins (ALP, RUNX2, BMP2, BMPR1, and BMPR2) than those in control MSC-EVs (C-EV). Besides, it was shown that T-EV not only regulated M1/M2 macrophages differentiation of monocytes, also effectively increased the osteogenic differentiation of MSCs as well as bone tissue regeneration in a bone defect rat model. Based on these results, it is concluded that TUDCA treatment to MSC as a new approach endows EV with high-yield production and functionality. Thus, we strongly believe T-EV would be a powerful therapeutic material for bone tissue regeneration and potentially could be expanded to other types of tissue regeneration for clinical applications.
MeSH term(s)	Rats ; Animals ; Osteogenesis ; Cytokines/metabolism ; Bone Regeneration ; Extracellular Vesicles/metabolism
Chemical Substances	ursodoxicoltaurine (60EUX8MN5X) ; Cytokines
Language	English
Publishing date	2023-01-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2022.12.053
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Article: Functional Duality of Chondrocyte Hypertrophy and Biomedical Application Trends in Osteoarthritis.

Park, Sunghyun / Bello, Alvin / Arai, Yoshie / Ahn, Jinsung / Kim, Dohyun / Cha, Kyung-Yup / Baek, Inho / Park, Hansoo / Lee, Soo-Hong

Pharmaceutics

2021 Volume 13, Issue 8

Abstract: Chondrocyte hypertrophy is one of the key indicators in the progression of osteoarthritis (OA). However, compared with other OA indications, such as cartilage collapse, sclerosis, inflammation, and protease activation, the mechanisms by which chondrocyte ...

Abstract	Chondrocyte hypertrophy is one of the key indicators in the progression of osteoarthritis (OA). However, compared with other OA indications, such as cartilage collapse, sclerosis, inflammation, and protease activation, the mechanisms by which chondrocyte hypertrophy contributes to OA remain elusive. As the pathological processes in the OA cartilage microenvironment, such as the alterations in the extracellular matrix, are initiated and dictated by the physiological state of the chondrocytes, in-depth knowledge of chondrocyte hypertrophy is necessary to enhance our understanding of the disease pathology and develop therapeutic agents. Chondrocyte hypertrophy is a factor that induces OA progression; it is also a crucial factor in the endochondral ossification. This review elaborates on this dual functionality of chondrocyte hypertrophy in OA progression and endochondral ossification through a description of the characteristics of various genes and signaling, their mechanism, and their distinguishable physiological effects. Chondrocyte hypertrophy in OA progression leads to a decrease in chondrogenic genes and destruction of cartilage tissue. However, in endochondral ossification, it represents an intermediate stage at the process of differentiation of chondrocytes into osteogenic cells. In addition, this review describes the current therapeutic strategies and their mechanisms, involving genes, proteins, cytokines, small molecules, three-dimensional environments, or exosomes, against the OA induced by chondrocyte hypertrophy. Finally, this review proposes that the contrasting roles of chondrocyte hypertrophy are essential for both OA progression and endochondral ossification, and that this cellular process may be targeted to develop OA therapeutics.
Language	English
Publishing date	2021-07-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics13081139
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Article ; Online: SPRY4 acts as an indicator of osteoarthritis severity and regulates chondrocyte hypertrophy and ECM protease expression.

Park, Sunghyun / Arai, Yoshie / Bello, Alvin / Park, Hansoo / Kim, Dohyun / Park, Kyung-Soon / Lee, Soo-Hong

NPJ Regenerative medicine

2021 Volume 6, Issue 1, Page(s) 56

Abstract: Osteoarthritis (OA) causes serious changes in the metabolic and signaling pathways of chondrocytes, including the mitogen-activated protein kinase (MAPK) pathway. However, the role of sprouty RTK signaling antagonist 4 (SPRY4), an inhibitor of MAPK, in ... ...

Abstract	Osteoarthritis (OA) causes serious changes in the metabolic and signaling pathways of chondrocytes, including the mitogen-activated protein kinase (MAPK) pathway. However, the role of sprouty RTK signaling antagonist 4 (SPRY4), an inhibitor of MAPK, in the human cartilage tissues and chondrocytes remains to be understood. Here, using SPRY4 gene delivery into healthy and degenerated chondrocytes, we elucidated the role of SPRY4 in preventing chondrocyte hypertrophy. In addition to using the human cartilage tissues with the destabilization of the medial meniscus (DMM) model in Sprague-Dawley (SD) rats, the role of SPRY4 in cartilage tissues and chondrocytes was explored through their molecular and histological analyses. In order to determine the effects of SPRY4 on healthy human chondrocyte hypertrophy, small interfering RNA (siRNA) was used to knock down SPRY4. Lentiviral transduction of SPRY4 into degenerated human chondrocytes allowed us to investigate its ability to prevent hypertrophy. SPRY4 expression levels were higher in healthy human cartilage tissue and chondrocytes than in degenerated human cartilage tissues and hypertrophy-induced chondrocytes. The knockdown of SPRY4 in healthy chondrocytes caused an increase in hypertrophy, senescence, reactive oxygen species (ROS) production, and extracellular matrix (ECM) protease expression. However, all these factors decreased upon overexpression of SPRY4 in degenerated chondrocytes via regulation of the MAPK signaling pathway. We conclude that SPRY4 is a crucial indicator of osteoarthritis (OA) severity and could play an important role in preventing OA in the cartilage by inhibiting chondrocyte hypertrophy.
Language	English
Publishing date	2021-09-17
Publishing country	United States
Document type	Journal Article
ISSN	2057-3995
ISSN (online)	2057-3995
DOI	10.1038/s41536-021-00165-9
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Article ; Online: Cryptic ligand on collagen matrix unveiled by MMP13 accelerates bone tissue regeneration via MMP13/Integrin α3/RUNX2 feedback loop.

Arai, Yoshie / Choi, Bogyu / Kim, Byoung Ju / Park, Sunghyun / Park, Hyoeun / Moon, James J / Lee, Soo-Hong

Acta biomaterialia

2021 Volume 125, Page(s) 219–230

Abstract: Extracellular matrix (ECM) remodeling is necessary for the development and self-healing of tissue, and the process is tissue specific. Matrix metalloproteinases (MMPs) play a role in ECM remodeling by unwinding and cleaving ECM. We hypothesized that ECM ... ...

Abstract	Extracellular matrix (ECM) remodeling is necessary for the development and self-healing of tissue, and the process is tissue specific. Matrix metalloproteinases (MMPs) play a role in ECM remodeling by unwinding and cleaving ECM. We hypothesized that ECM remodeling by MMPs is involved in the differentiation of stem cells into specific lineages during self-healing. To prove the hypothesis, we investigated which MMPs are involved in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) grown on a type I collagen (Col I) matrix, and we found that specifically high expression of MMP13 in hMSCs grown on a Col I matirx during osteogenic differentiation. Moreover, knocking down of MMP13 decreased the osteogenic differentiation of hMSCs grown on a Col I matrix. In addition, pre-treatment of recombinant human MMP13 lead to remodeling of Col I matrix and increased the osteogenic differentiation of hMSCs and in vivo bone formation following the upregulation of the expression of runt-related transcription factor 2 (RUNX2), integrin α3 (ITGA3), and focal adhesion kinase. Furthermore, the transcription factor RUNX2 bound to the MMP13 promoter. These results suggest that growth on a remodeled Col I matrix by MMP13 stimulates osteogenic differentiation of hMSCs and self-healing of bone tissue via an MMP13/ITGA3/RUNX2 positive feedback loop. STATEMENT OF SIGNIFICANCE: Self-healing of tissue could be the key to treating diseases that cannot be overcome by present technology. We investigated the mechanism underlying the self-healing of tissue and we found that the osteogenic differentiation was increased in hMSCs grown on a remodeled Col I matrix by the optimized concentration of MMP13 not in hMSCs grown on a Col I fragments cleaved by a high concentration of MMP13. In addition, we found the remodeled Col I matrix by MMP13 increased the osteogenic capacity through a MMP13/integrin α3/RUNX2 positive feedback loop. This result would be able to not only provide a strategy for bone tissue-specific functional materials following strong evidence about the self-healing mechanism of bone through the interaction between stem cells and the ECM matrix. As such, we strongly believe our finding will be of interest to researchers studying biomaterials, stem cell biology and matrix interaction for regenerative medicine and therapy.
MeSH term(s)	Bone Regeneration ; Bone and Bones ; Cell Differentiation ; Cells, Cultured ; Collagen ; Core Binding Factor Alpha 1 Subunit/genetics ; Feedback ; Humans ; Integrin alpha3 ; Ligands ; Matrix Metalloproteinase 13/genetics ; Mesenchymal Stem Cells ; Osteogenesis
Chemical Substances	Core Binding Factor Alpha 1 Subunit ; Integrin alpha3 ; Ligands ; RUNX2 protein, human ; Collagen (9007-34-5) ; MMP13 protein, human (EC 3.4.24.-) ; Matrix Metalloproteinase 13 (EC 3.4.24.-)
Language	English
Publishing date	2021-03-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2021.02.042
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Article: Tauroursodeoxycholic acid (TUDCA) counters osteoarthritis by regulating intracellular cholesterol levels and membrane fluidity of degenerated chondrocytes

Arai, Yoshie / Ahn, Jinsung / Choi, Bogyu / Kim, Byoung Ju / Lee, Soo-Hong / Park, Hyoeun / Park, Sunghyun / Rim, Wongyu

Biomaterials science. 2019 July 23, v. 7, no. 8

2019

Abstract: Cholesterol and lipid metabolism are associated with osteoarthritis (OA) in human cartilage. High cholesterol levels in OA chondrocytes leads to decreased membrane fluidity and blocks the signaling cascade associated with the expression of chondrogenic ... ...

Abstract	Cholesterol and lipid metabolism are associated with osteoarthritis (OA) in human cartilage. High cholesterol levels in OA chondrocytes leads to decreased membrane fluidity and blocks the signaling cascade associated with the expression of chondrogenic genes. It is known that bile acid plays a role in regulating cholesterol homeostasis and the digestion of fats in the human body. Tauroursodeoxycholic acid (TUDCA), as a member of the bile acid family, also aids in the transport of cellular cholesterol. In this study, we hypothesized that TUDCA might be able to promote the restoration of OA cartilage by reducing membrane cholesterol levels in OA chondrocytes and by stimulating the chondrogenic signaling cascade. To assess this hypothesis, we investigated the effects of TUDCA on degenerated chondrocytes isolated from patients with OA. Importantly, treatment with TUDCA at sub-micellar concentrations (2500 μM) significantly increased cell proliferation and Cyclin D1 expression compared with the controls. In addition, the expression of chondrogenic marker genes (SOX9, COL2, and ACAN), proteins (SOX9 and COL2), and glycosaminoglycan (Chondroitin sulfate) was much higher in the TUDCA-treated group compared to the controls. We also found that TUDCA treatment significantly reduced the intracellular cholesterol levels in the chondrocytes and increased membrane fluidity. Furthermore, the stability of TGF receptor 1 and activity of focal adhesion proteins were also increased following TUDCA treatment. Together, these results demonstrated that TUDCA could be used as an alternative treatment for the restoration of OA cartilage.
Keywords	bile acids ; cartilage ; cell proliferation ; cholesterol ; chondrocytes ; chondroitin sulfate ; counters ; cyclins ; digestion ; focal adhesions ; genes ; genetic markers ; homeostasis ; humans ; lipid metabolism ; membrane fluidity ; osteoarthritis ; patients
Language	English
Dates of publication	2019-0723
Size	p. 3178-3189.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/c9bm00426b
Database	NAL-Catalogue (AGRICOLA)

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