3024 Osteocyte-derived CXCL12 is Essential for Load-Induced Bone Formation in Adult Mice
OBJECTIVES/SPECIFIC AIMS: Our aim is to test whether osteocyte-specific CXCL12 expression is critical to exercise-driven bone formation. METHODS/STUDY POPULATION: All procedures were approved by the NEW YORK UNIVERSITY Institutional Animal Care and Use Committee. We generated male and female mice in...
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2019-03-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866119002541/type/journal_article |
| _version_ | 1811156603867496448 |
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| author | Pamela Cabahug Zuckerman Chao Liu Emily Fang Alesha B Castillo |
| author_facet | Pamela Cabahug Zuckerman Chao Liu Emily Fang Alesha B Castillo |
| author_sort | Pamela Cabahug Zuckerman |
| collection | DOAJ |
| description | OBJECTIVES/SPECIFIC AIMS: Our aim is to test whether osteocyte-specific CXCL12 expression is critical to exercise-driven bone formation. METHODS/STUDY POPULATION: All procedures were approved by the NEW YORK UNIVERSITY Institutional Animal Care and Use Committee. We generated male and female mice in which CXCL12 was deleted from OCYs (CXCL12ΔOCY) by crossing CXCL12 floxed mice and 10kb DMP1-Cre transgenic mice (gifts from Drs. Geoffrey Gurtner and Lynda Bonewald, respectively). The 10kb DMP1-Cre has been shown to be robustly expressed in odontoblasts and OCYs, with little to no activity in cells from non-mineralized tissues (Lu+ J Dent Res 2007). Growing male and female mice (n=3-8/group) were given fluorochrome labels every two weeks between 4-16 weeks of age, to monitor the role of CXCL12 during development. A second group, of adult 16-week-old mice (n=5/group), were subjected to tibial axial cyclic loading (1200µɛ, 2Hz, 120cycles, 3days/wk for 2 wks) (Liu+ Bone 2018). Basal and load-induced periosteal (Ps) and endosteal (Es) mineralizing surface (MS/BS, %), mineral apposition (MAR, µm/day) and bone formation rates (BFR/BS, µm3/µm2/year) were calculated (Dempster+ JBMR.2013) at mid-length. RESULTS/ANTICIPATED RESULTS: No significant differences were detected in basal bone formation during development. However, relative load-induced Ps MAR (rMAR) was reduced by 50% in female (p=0.02) and 75% in male (p=0.002) CXCL12ΔOCY mice; and similarly, Ps rBFR/BS was reduced by 50% in female (p=0.01) and 70% in male (p=0.001) CXCL12ΔOCY mice (Figure 1). Es bone formation was not affected by CXCL12 deletion. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, osteocyte-specific CXCL12 expression plays a critical role in exercise-driven periosteal new bone formation, suggesting that CXCL12 signaling may positively regulate osteogenic differentiation and/or mature osteoblast function. Further underlying mechanisms are currently being explored. Thus, osteocyte-specific CXCL12 signaling may be a promising target to enhance load-induced bone formation in patients with compromised ability to form new bone. |
| first_indexed | 2024-04-10T04:54:10Z |
| format | Article |
| id | doaj.art-cc219cdddf1544bbb46aa15a8f15f008 |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-10T04:54:10Z |
| publishDate | 2019-03-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-cc219cdddf1544bbb46aa15a8f15f0082023-03-09T12:30:31ZengCambridge University PressJournal of Clinical and Translational Science2059-86612019-03-01311111110.1017/cts.2019.2543024 Osteocyte-derived CXCL12 is Essential for Load-Induced Bone Formation in Adult MicePamela Cabahug Zuckerman0Chao Liu1Emily Fang2Alesha B Castillo3New York University - H+H Clinical and Translational Science InstituteNew York University - H+H Clinical and Translational Science InstituteNew York University - H+H Clinical and Translational Science InstituteNew York University - H+H Clinical and Translational Science InstituteOBJECTIVES/SPECIFIC AIMS: Our aim is to test whether osteocyte-specific CXCL12 expression is critical to exercise-driven bone formation. METHODS/STUDY POPULATION: All procedures were approved by the NEW YORK UNIVERSITY Institutional Animal Care and Use Committee. We generated male and female mice in which CXCL12 was deleted from OCYs (CXCL12ΔOCY) by crossing CXCL12 floxed mice and 10kb DMP1-Cre transgenic mice (gifts from Drs. Geoffrey Gurtner and Lynda Bonewald, respectively). The 10kb DMP1-Cre has been shown to be robustly expressed in odontoblasts and OCYs, with little to no activity in cells from non-mineralized tissues (Lu+ J Dent Res 2007). Growing male and female mice (n=3-8/group) were given fluorochrome labels every two weeks between 4-16 weeks of age, to monitor the role of CXCL12 during development. A second group, of adult 16-week-old mice (n=5/group), were subjected to tibial axial cyclic loading (1200µɛ, 2Hz, 120cycles, 3days/wk for 2 wks) (Liu+ Bone 2018). Basal and load-induced periosteal (Ps) and endosteal (Es) mineralizing surface (MS/BS, %), mineral apposition (MAR, µm/day) and bone formation rates (BFR/BS, µm3/µm2/year) were calculated (Dempster+ JBMR.2013) at mid-length. RESULTS/ANTICIPATED RESULTS: No significant differences were detected in basal bone formation during development. However, relative load-induced Ps MAR (rMAR) was reduced by 50% in female (p=0.02) and 75% in male (p=0.002) CXCL12ΔOCY mice; and similarly, Ps rBFR/BS was reduced by 50% in female (p=0.01) and 70% in male (p=0.001) CXCL12ΔOCY mice (Figure 1). Es bone formation was not affected by CXCL12 deletion. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, osteocyte-specific CXCL12 expression plays a critical role in exercise-driven periosteal new bone formation, suggesting that CXCL12 signaling may positively regulate osteogenic differentiation and/or mature osteoblast function. Further underlying mechanisms are currently being explored. Thus, osteocyte-specific CXCL12 signaling may be a promising target to enhance load-induced bone formation in patients with compromised ability to form new bone.https://www.cambridge.org/core/product/identifier/S2059866119002541/type/journal_article |
| spellingShingle | Pamela Cabahug Zuckerman Chao Liu Emily Fang Alesha B Castillo 3024 Osteocyte-derived CXCL12 is Essential for Load-Induced Bone Formation in Adult Mice Journal of Clinical and Translational Science |
| title | 3024 Osteocyte-derived CXCL12 is Essential for Load-Induced Bone Formation in Adult Mice |
| title_full | 3024 Osteocyte-derived CXCL12 is Essential for Load-Induced Bone Formation in Adult Mice |
| title_fullStr | 3024 Osteocyte-derived CXCL12 is Essential for Load-Induced Bone Formation in Adult Mice |
| title_full_unstemmed | 3024 Osteocyte-derived CXCL12 is Essential for Load-Induced Bone Formation in Adult Mice |
| title_short | 3024 Osteocyte-derived CXCL12 is Essential for Load-Induced Bone Formation in Adult Mice |
| title_sort | 3024 osteocyte derived cxcl12 is essential for load induced bone formation in adult mice |
| url | https://www.cambridge.org/core/product/identifier/S2059866119002541/type/journal_article |
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