C-C Motif Chemokine Ligand 2 Enhances Macrophage Chemotaxis, Osteogenesis, and Angiogenesis during the Inflammatory Phase of Bone Regeneration
Local cell therapy has recently gained attention for the treatment of joint diseases and fractures. Mesenchymal stem cells (MSCs) are not only involved in osteogenesis and angiogenesis, but they also have immunomodulatory functions, such as inducing macrophage migration during bone regeneration via macrophage crosstalk. C-C motif chemokine ligand 2 (CCL2), a known inflammatory mediator, is associated with the migration of macrophages during inflammation. This study examined the utility of CCL2 as a therapeutic target for local cell therapy. Using lentiviral vectors for rabbit MSCs, genetically modified CCL2 overexpressing MSCs were generated. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture, and cell migration assays were also performed. Additionally, co-cultures were performed with endothelial cells (ECs), and angiogenesis was evaluated using a tube formation assay. Overexpression of CCL2 did not affect bone formation under monoculture conditions but promoted chemotaxis and osteogenesis when co-cultured with macrophages. Furthermore, CCL2-overexpression promoted tube formation in co-culture with ECs. These results suggest that CCL2 induces macrophage chemotaxis and osteogenesis by promoting crosstalk between MSCs and macrophages; CCL2 also stimulates ECs to induce angiogenesis. These findings indicate that CCL2 may be a useful therapeutic target for local cell therapy in areas of bone loss.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
---|---|
Enthalten in: |
Biomolecules - 13(2023), 11 vom: 18. Nov. |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Shinohara, Issei [VerfasserIn] |
---|
Links: |
---|
Themen: |
Angiogenesis |
---|
Anmerkungen: |
Date Completed 27.11.2023 Date Revised 04.01.2024 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.3390/biom13111665 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM364935642 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM364935642 | ||
003 | DE-627 | ||
005 | 20240108141713.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/biom13111665 |2 doi | |
028 | 5 | 2 | |a pubmed24n1248.xml |
035 | |a (DE-627)NLM364935642 | ||
035 | |a (NLM)38002347 | ||
035 | |a (PII)1665 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Shinohara, Issei |e verfasserin |4 aut | |
245 | 1 | 0 | |a C-C Motif Chemokine Ligand 2 Enhances Macrophage Chemotaxis, Osteogenesis, and Angiogenesis during the Inflammatory Phase of Bone Regeneration |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 27.11.2023 | ||
500 | |a Date Revised 04.01.2024 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Local cell therapy has recently gained attention for the treatment of joint diseases and fractures. Mesenchymal stem cells (MSCs) are not only involved in osteogenesis and angiogenesis, but they also have immunomodulatory functions, such as inducing macrophage migration during bone regeneration via macrophage crosstalk. C-C motif chemokine ligand 2 (CCL2), a known inflammatory mediator, is associated with the migration of macrophages during inflammation. This study examined the utility of CCL2 as a therapeutic target for local cell therapy. Using lentiviral vectors for rabbit MSCs, genetically modified CCL2 overexpressing MSCs were generated. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture, and cell migration assays were also performed. Additionally, co-cultures were performed with endothelial cells (ECs), and angiogenesis was evaluated using a tube formation assay. Overexpression of CCL2 did not affect bone formation under monoculture conditions but promoted chemotaxis and osteogenesis when co-cultured with macrophages. Furthermore, CCL2-overexpression promoted tube formation in co-culture with ECs. These results suggest that CCL2 induces macrophage chemotaxis and osteogenesis by promoting crosstalk between MSCs and macrophages; CCL2 also stimulates ECs to induce angiogenesis. These findings indicate that CCL2 may be a useful therapeutic target for local cell therapy in areas of bone loss | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a CCL2 | |
650 | 4 | |a MSCs | |
650 | 4 | |a angiogenesis | |
650 | 4 | |a inflammation | |
650 | 4 | |a macrophage | |
650 | 4 | |a migration | |
650 | 4 | |a osteogenesis | |
650 | 7 | |a Ligands |2 NLM | |
700 | 1 | |a Tsubosaka, Masanori |e verfasserin |4 aut | |
700 | 1 | |a Toya, Masakazu |e verfasserin |4 aut | |
700 | 1 | |a Lee, Max L |e verfasserin |4 aut | |
700 | 1 | |a Kushioka, Junichi |e verfasserin |4 aut | |
700 | 1 | |a Murayama, Masatoshi |e verfasserin |4 aut | |
700 | 1 | |a Gao, Qi |e verfasserin |4 aut | |
700 | 1 | |a Li, Xueping |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Ning |e verfasserin |4 aut | |
700 | 1 | |a Chow, Simon Kwoon-Ho |e verfasserin |4 aut | |
700 | 1 | |a Matsumoto, Tomoyuki |e verfasserin |4 aut | |
700 | 1 | |a Kuroda, Ryosuke |e verfasserin |4 aut | |
700 | 1 | |a Goodman, Stuart B |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Biomolecules |d 2011 |g 13(2023), 11 vom: 18. Nov. |w (DE-627)NLM228347106 |x 2218-273X |7 nnns |
773 | 1 | 8 | |g volume:13 |g year:2023 |g number:11 |g day:18 |g month:11 |
856 | 4 | 0 | |u http://dx.doi.org/10.3390/biom13111665 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 13 |j 2023 |e 11 |b 18 |c 11 |