JD-312 – A novel small molecule that facilitates cartilage repair and alleviates osteoarthritis progression
Background: The chondrogenic differentiation of mesenchymal stem cells (MSCs) to enhance cartilage repair and regeneration is a promising strategy to alleviate osteoarthritis (OA) progression. Method: The potency of JD-312 in inducing chondrogenic differentiation of MSCs was assessed and verified. The efficacy of JD-312-treated MSCs was evaluated using a Sprague–Dawley rat DMM model. Additionally, the capacity of JD-312 to successfully recruit bone marrow-derived mesenchymal stem cells (BMSCs) for the treatment of OA in vitro was confirmed via intra-articular injection. The repair status of the articular cartilage was analyzed in vivo through histological examination. Result: In this study, we identify JD-312 as a novel non-toxic small molecule that can promote chondrogenic differentiation in human umbilical cord-derived MSCs (hUCMSCs) and human bone marrow MSCS (hBMSCs) in vitro. We also show that transient differentiation of MSCs with JD-312 prior to in vivo administration remarkably improves the regeneration of cartilage and promotes Col2a1 and Acan expression in rat models of DMM, in comparison to kartogenin (KGN) pre-treatment or MSCs alone. Furthermore, direct intra-articular injection of JD-312 in murine model of OA showed reduced loss of articular cartilage and improved pain parameters. Lastly, we identified that the effects of JD-312 are at least in part mediated via upregulation of genes associated with the focal adhesion, PI3K-Akt signaling and the ECM-receptor interaction pathways, and specifically cartilage oligomeric matrix protein (COMP) may play a vital role. Conclusion: Our study demonstrated that JD-312 showed encouraging repair effects for OA in vivo. The translational potential of this article: Together, our findings demonstrate that JD-312 is a promising new therapeutic molecule for cartilage regeneration with clinical potential..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:44 |
|---|---|
| Enthalten in: |
Journal of Orthopaedic Translation - 44(2024), Seite 60-71 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jingduo Gao [VerfasserIn] |
|---|
| Links: |
doi.org [kostenfrei] |
|---|
| Themen: |
Cartilage |
|---|
| doi: |
10.1016/j.jot.2023.11.007 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
DOAJ097944777 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ097944777 | ||
| 003 | DE-627 | ||
| 005 | 20240414201354.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240413s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jot.2023.11.007 |2 doi | |
| 035 | |a (DE-627)DOAJ097944777 | ||
| 035 | |a (DE-599)DOAJ0a495d8d789d48189e227d356192631d | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a RC925-935 | |
| 100 | 0 | |a Jingduo Gao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a JD-312 – A novel small molecule that facilitates cartilage repair and alleviates osteoarthritis progression |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Background: The chondrogenic differentiation of mesenchymal stem cells (MSCs) to enhance cartilage repair and regeneration is a promising strategy to alleviate osteoarthritis (OA) progression. Method: The potency of JD-312 in inducing chondrogenic differentiation of MSCs was assessed and verified. The efficacy of JD-312-treated MSCs was evaluated using a Sprague–Dawley rat DMM model. Additionally, the capacity of JD-312 to successfully recruit bone marrow-derived mesenchymal stem cells (BMSCs) for the treatment of OA in vitro was confirmed via intra-articular injection. The repair status of the articular cartilage was analyzed in vivo through histological examination. Result: In this study, we identify JD-312 as a novel non-toxic small molecule that can promote chondrogenic differentiation in human umbilical cord-derived MSCs (hUCMSCs) and human bone marrow MSCS (hBMSCs) in vitro. We also show that transient differentiation of MSCs with JD-312 prior to in vivo administration remarkably improves the regeneration of cartilage and promotes Col2a1 and Acan expression in rat models of DMM, in comparison to kartogenin (KGN) pre-treatment or MSCs alone. Furthermore, direct intra-articular injection of JD-312 in murine model of OA showed reduced loss of articular cartilage and improved pain parameters. Lastly, we identified that the effects of JD-312 are at least in part mediated via upregulation of genes associated with the focal adhesion, PI3K-Akt signaling and the ECM-receptor interaction pathways, and specifically cartilage oligomeric matrix protein (COMP) may play a vital role. Conclusion: Our study demonstrated that JD-312 showed encouraging repair effects for OA in vivo. The translational potential of this article: Together, our findings demonstrate that JD-312 is a promising new therapeutic molecule for cartilage regeneration with clinical potential. | ||
| 650 | 4 | |a Small molecule | |
| 650 | 4 | |a MSCs | |
| 650 | 4 | |a Osteoarthritis | |
| 650 | 4 | |a Cartilage | |
| 650 | 4 | |a Regeneration | |
| 650 | 4 | |a Repair | |
| 653 | 0 | |a Diseases of the musculoskeletal system | |
| 700 | 0 | |a Haixiang Pei |e verfasserin |4 aut | |
| 700 | 0 | |a Fang Lv |e verfasserin |4 aut | |
| 700 | 0 | |a Xin Niu |e verfasserin |4 aut | |
| 700 | 0 | |a Yu You |e verfasserin |4 aut | |
| 700 | 0 | |a Liang He |e verfasserin |4 aut | |
| 700 | 0 | |a Shijia Hu |e verfasserin |4 aut | |
| 700 | 0 | |a Karan M. Shah |e verfasserin |4 aut | |
| 700 | 0 | |a Mingyao Liu |e verfasserin |4 aut | |
| 700 | 0 | |a Yihua Chen |e verfasserin |4 aut | |
| 700 | 0 | |a Bing Du |e verfasserin |4 aut | |
| 700 | 0 | |a Hai Xiong |e verfasserin |4 aut | |
| 700 | 0 | |a Jian Luo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Journal of Orthopaedic Translation |d Elsevier, 2016 |g 44(2024), Seite 60-71 |w (DE-627)DOAJ000146536 |x 22140328 |7 nnns |
| 773 | 1 | 8 | |g volume:44 |g year:2024 |g pages:60-71 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.jot.2023.11.007 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/0a495d8d789d48189e227d356192631d |z kostenfrei |
| 856 | 4 | 0 | |u http://www.sciencedirect.com/science/article/pii/S2214031X23000955 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/2214-031X |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 951 | |a AR | ||
| 952 | |d 44 |j 2024 |h 60-71 | ||