CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic Osteoarthritis
In osteoarthritis (OA), bone changes are radiological hallmarks and are considered important for disease progression. The C-C chemokine receptor-2 (CCR2) has been shown to play an important role in bone physiology. In this study, we investigated whether <i>Ccr2</i> osteoblast-specific in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/6/891 |
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| author | Helen Willcockson Huseyin Ozkan José Valdés-Fernández Liubov Arbeeva Esra Mucahit Layla Musawwir Lola B. Hooper Froilán Granero-Moltó Felipe Prósper Lara Longobardi |
| author_facet | Helen Willcockson Huseyin Ozkan José Valdés-Fernández Liubov Arbeeva Esra Mucahit Layla Musawwir Lola B. Hooper Froilán Granero-Moltó Felipe Prósper Lara Longobardi |
| author_sort | Helen Willcockson |
| collection | DOAJ |
| description | In osteoarthritis (OA), bone changes are radiological hallmarks and are considered important for disease progression. The C-C chemokine receptor-2 (CCR2) has been shown to play an important role in bone physiology. In this study, we investigated whether <i>Ccr2</i> osteoblast-specific inactivation at different times during post-traumatic OA (PTOA) progression improves joint structures, bone parameters, and pain. We used a tamoxifen-inducible <i>Ccr2</i> inactivation in Collagen1α-expressing cells to obtain osteoblasts lacking <i>Ccr2</i> (<i>CCR2</i>-<i>Col1αKO</i>). We stimulated PTOA changes in <i>CCR2</i>-<i>Col1αKO</i> and <i>CCR2</i>+/+ mice using the destabilization of the meniscus model (DMM), inducing recombination before or after DMM (early- vs. late-inactivation). Joint damage was evaluated at two, four, eight, and twelve weeks post-DMM using multiple scores: articular-cartilage structure (ACS), Safranin-O, histomorphometry, osteophyte size/maturity, subchondral bone thickness and synovial hyperplasia. Spontaneous and evoked pain were assessed for up to 20 weeks. We found that early osteoblast-<i>Ccr2</i> inactivation delayed articular cartilage damage and matrix degeneration compared to <i>CCR2</i>+/+, as well as DMM-induced bone thickness. Osteophyte formation and maturation were only minimally affected. Late Collagen1α-<i>Ccr2</i> deletion led to less evident improvements. Osteoblast-<i>Ccr2</i> deletion also improved static measures of pain, while evoked pain did not change. Our study demonstrates that <i>Ccr2</i> expression in osteoblasts contributes to PTOA disease progression and pain by affecting both cartilage and bone tissues. |
| first_indexed | 2024-03-11T02:43:04Z |
| format | Article |
| id | doaj.art-c127a3c704f94e52971577197b42310a |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T02:43:04Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-c127a3c704f94e52971577197b42310a2023-11-18T09:30:16ZengMDPI AGBiomolecules2218-273X2023-05-0113689110.3390/biom13060891CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic OsteoarthritisHelen Willcockson0Huseyin Ozkan1José Valdés-Fernández2Liubov Arbeeva3Esra Mucahit4Layla Musawwir5Lola B. Hooper6Froilán Granero-Moltó7Felipe Prósper8Lara Longobardi9Division of Rheumatology, Allergy and Immunology, University of North Carolina at Chapel Hill, 3300 Thurston Bldg, Campus Box 7280, Chapel Hill, NC 27599, USADivision of Rheumatology, Allergy and Immunology, University of North Carolina at Chapel Hill, 3300 Thurston Bldg, Campus Box 7280, Chapel Hill, NC 27599, USAProgram of Regenerative Medicine, Center for Applied Medical Research (CIMA), Universidad de Navarra, 31008 Pamplona, SpainDivision of Rheumatology, Allergy and Immunology, University of North Carolina at Chapel Hill, 3300 Thurston Bldg, Campus Box 7280, Chapel Hill, NC 27599, USADivision of Rheumatology, Allergy and Immunology, University of North Carolina at Chapel Hill, 3300 Thurston Bldg, Campus Box 7280, Chapel Hill, NC 27599, USADivision of Rheumatology, Allergy and Immunology, University of North Carolina at Chapel Hill, 3300 Thurston Bldg, Campus Box 7280, Chapel Hill, NC 27599, USADivision of Rheumatology, Allergy and Immunology, University of North Carolina at Chapel Hill, 3300 Thurston Bldg, Campus Box 7280, Chapel Hill, NC 27599, USAProgram of Regenerative Medicine, Center for Applied Medical Research (CIMA), Universidad de Navarra, 31008 Pamplona, SpainProgram of Regenerative Medicine, Center for Applied Medical Research (CIMA), Universidad de Navarra, 31008 Pamplona, SpainDivision of Rheumatology, Allergy and Immunology, University of North Carolina at Chapel Hill, 3300 Thurston Bldg, Campus Box 7280, Chapel Hill, NC 27599, USAIn osteoarthritis (OA), bone changes are radiological hallmarks and are considered important for disease progression. The C-C chemokine receptor-2 (CCR2) has been shown to play an important role in bone physiology. In this study, we investigated whether <i>Ccr2</i> osteoblast-specific inactivation at different times during post-traumatic OA (PTOA) progression improves joint structures, bone parameters, and pain. We used a tamoxifen-inducible <i>Ccr2</i> inactivation in Collagen1α-expressing cells to obtain osteoblasts lacking <i>Ccr2</i> (<i>CCR2</i>-<i>Col1αKO</i>). We stimulated PTOA changes in <i>CCR2</i>-<i>Col1αKO</i> and <i>CCR2</i>+/+ mice using the destabilization of the meniscus model (DMM), inducing recombination before or after DMM (early- vs. late-inactivation). Joint damage was evaluated at two, four, eight, and twelve weeks post-DMM using multiple scores: articular-cartilage structure (ACS), Safranin-O, histomorphometry, osteophyte size/maturity, subchondral bone thickness and synovial hyperplasia. Spontaneous and evoked pain were assessed for up to 20 weeks. We found that early osteoblast-<i>Ccr2</i> inactivation delayed articular cartilage damage and matrix degeneration compared to <i>CCR2</i>+/+, as well as DMM-induced bone thickness. Osteophyte formation and maturation were only minimally affected. Late Collagen1α-<i>Ccr2</i> deletion led to less evident improvements. Osteoblast-<i>Ccr2</i> deletion also improved static measures of pain, while evoked pain did not change. Our study demonstrates that <i>Ccr2</i> expression in osteoblasts contributes to PTOA disease progression and pain by affecting both cartilage and bone tissues.https://www.mdpi.com/2218-273X/13/6/891chemokinesboneosteoarthritis |
| spellingShingle | Helen Willcockson Huseyin Ozkan José Valdés-Fernández Liubov Arbeeva Esra Mucahit Layla Musawwir Lola B. Hooper Froilán Granero-Moltó Felipe Prósper Lara Longobardi CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic Osteoarthritis Biomolecules chemokines bone osteoarthritis |
| title | CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic Osteoarthritis |
| title_full | CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic Osteoarthritis |
| title_fullStr | CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic Osteoarthritis |
| title_full_unstemmed | CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic Osteoarthritis |
| title_short | CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic Osteoarthritis |
| title_sort | cc chemokine receptor 2 expression in osteoblasts contributes to cartilage and bone damage during post traumatic osteoarthritis |
| topic | chemokines bone osteoarthritis |
| url | https://www.mdpi.com/2218-273X/13/6/891 |
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