lncRNA-CRNDE regulates BMSC chondrogenic differentiation and promotes cartilage repair in osteoarthritis through SIRT1/SOX9

Although BMSC-based therapy is one of the most front-line technologies for cartilage repair, it is still a big challenge to attain ideal niches for BMSC chondrogenic differentiation.

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Enhanced Chondrogenic Differentiation Activities in Human Bone Marrow Aspirates via sox9 Overexpression Mediated by pNaSS-Grafted PCL Film-Guided rAAV Gene Transfer

Pharmaceutics ◽

10.3390/pharmaceutics12030280 ◽

2020 ◽

Vol 12 (3) ◽

pp. 280 ◽

Cited By ~ 3

Author(s):

Jagadeesh K. Venkatesan ◽

Weikun Meng ◽

Ana Rey-Rico ◽

Gertrud Schmitt ◽

Susanne Speicher-Mentges ◽

...

Keyword(s):

Bone Marrow ◽

Cartilage Repair ◽

Chondrogenic Differentiation ◽

High Mobility ◽

Adeno Associated Virus ◽

Matrix Deposition ◽

Non Invasive ◽

Sodium Styrene Sulfonate ◽

Chondrogenic Potential ◽

Articular Cartilage Lesions

Background: The delivery of therapeutic genes in sites of articular cartilage lesions using non-invasive, scaffold-guided gene therapy procedures is a promising approach to stimulate cartilage repair while protecting the cargos from detrimental immune responses, particularly when targeting chondroreparative bone marrow-derived mesenchymal stromal cells in a natural microenvironment like marrow aspirates. Methods: Here, we evaluated the benefits of providing a sequence for the cartilage-specific sex-determining region Y-type high-mobility group box 9 (SOX9) transcription factor to human marrow aspirates via recombinant adeno-associated virus (rAAV) vectors delivered by poly(ε-caprolactone) (PCL) films functionalized via grafting with poly(sodium styrene sulfonate) (pNaSS) to enhance the marrow chondrogenic potential over time. Results: Effective sox9 overexpression was observed in aspirates treated with pNaSS-grafted or ungrafted PCL films coated with the candidate rAAV-FLAG-hsox9 (FLAG-tagged rAAV vector carrying a human sox9 gene sequence) vector for at least 21 days relative to other conditions (pNaSS-grafted and ungrafted PCL films without vector coating). Overexpression of sox9 via rAAV sox9/pNaSS-grafted or ungrafted PCL films led to increased biological and chondrogenic differentiation activities (matrix deposition) in the aspirates while containing premature osteogenesis and hypertrophy without impacting cell proliferation, with more potent effects noted when using pNaSS-grafted films. Conclusions: These findings show the benefits of targeting patients’ bone marrow via PCL film-guided therapeutic rAAV (sox9) delivery as an off-the-shelf system for future strategies to enhance cartilage repair in translational applications.

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Cartilage Protective and Chondrogenic Capacity of WIN-34B, a New Herbal Agent, in the Collagenase-Induced Osteoarthritis Rabbit Model and in Progenitor Cells from Subchondral Bone

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/527561 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Jeong-Eun Huh ◽

Yeon-Cheol Park ◽

Byung-Kwan Seo ◽

Jae-Dong Lee ◽

Yong-Hyeon Baek ◽

...

Keyword(s):

Progenitor Cells ◽

Cartilage Repair ◽

Subchondral Bone ◽

Chondrogenic Differentiation ◽

Rabbit Model ◽

Type Ii Collagen ◽

Blue Staining ◽

Vehicle Group ◽

Potential Candidate ◽

Type Ii

We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecanin vivoand was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagenin vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105) cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type IIα1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.

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Articular chondrocyte-derived exosomes promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

10.21203/rs.3.rs-23463/v2 ◽

2020 ◽

Author(s):

Ke Ma ◽

Bo Zhu ◽

Zetao Wang ◽

Peian Cai ◽

Mingwei He ◽

...

Keyword(s):

Stem Cells ◽

Umbilical Cord ◽

Cartilage Repair ◽

Chondrogenic Differentiation ◽

Phenotypic Expression ◽

Cartilage Regeneration ◽

Human Umbilical Cord ◽

Articular Chondrocyte ◽

Differentiation And Proliferation

Abstract Background Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that exosomes could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived exosomes (C-EXOs) in chondrogenic differentiation of HUCMSCs has not been reported. Results In this study, we successfully isolated chondrocyte-derived exosomes (C-EXO) from human multi-finger cartilage and found that C-EXO efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A and SOX-9. Also, the expression of the fibrotic marker, COL1A and hypertrophic marker, COL10, was significantly lower than that induced by TGF-β. In vivo, stimulation of C-EXO accelerated HUCMSCs-mediated cartilage repair in rabbit models. Furthermore, C-EXO led to increasing autophagosomes during the process of chondrogenic differentiation, indicating that C-EXO promoted cartilage regeneration might be through the activation of autophagy. Conclusions C-EXOs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.

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