Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing
Bone formation as well as bone healing capacity is known to be impaired in the elderly. Although bone formation is outpaced by bone resorption in aged individuals, we hereby present a novel path that considerably impacts bone formation and architecture: Bone formation is substantially reduced in age...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00797/full |
| _version_ | 1811240086988128256 |
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| author | Christian H. Bucher Christian H. Bucher Claudia Schlundt Claudia Schlundt Dag Wulsten F. Andrea Sass F. Andrea Sass Sebastian Wendler Sebastian Wendler Agnes Ellinghaus Tobias Thiele Ricarda Seemann Bettina M. Willie Hans-Dieter Volk Hans-Dieter Volk Georg N. Duda Georg N. Duda Georg N. Duda Katharina Schmidt-Bleek Katharina Schmidt-Bleek |
| author_facet | Christian H. Bucher Christian H. Bucher Claudia Schlundt Claudia Schlundt Dag Wulsten F. Andrea Sass F. Andrea Sass Sebastian Wendler Sebastian Wendler Agnes Ellinghaus Tobias Thiele Ricarda Seemann Bettina M. Willie Hans-Dieter Volk Hans-Dieter Volk Georg N. Duda Georg N. Duda Georg N. Duda Katharina Schmidt-Bleek Katharina Schmidt-Bleek |
| author_sort | Christian H. Bucher |
| collection | DOAJ |
| description | Bone formation as well as bone healing capacity is known to be impaired in the elderly. Although bone formation is outpaced by bone resorption in aged individuals, we hereby present a novel path that considerably impacts bone formation and architecture: Bone formation is substantially reduced in aged individual owing to the experience of the adaptive immunity. Thus, immune-aging in addition to chronological aging is a potential risk factor, with an experienced immune system being recognized as more pro-inflammatory. The role of the aging immune system on bone homeostasis and on the bone healing cascade has so far not been considered. Within this study mice at different age and immunological experience were analyzed toward bone properties. Healing was assessed by introducing an osteotomy, immune cells were adoptively transferred to disclose the difference in biological vs. chronological aging. In vitro studies were employed to test the interaction of immune cell products (cytokines) on cells of the musculoskeletal system. In metaphyseal bone, immune-aging affects bone homeostasis by impacting bone formation capacity and thereby influencing mass and microstructure of bone trabeculae leading to an overall reduced mechanical competence as found in bone torsional testing. Furthermore, bone formation is also impacted during bone regeneration in terms of a diminished healing capacity observed in young animals who have an experienced human immune system. We show the impact of an experienced immune system compared to a naïve immune system, demonstrating the substantial differences in the healing capacity and bone homeostasis due to the immune composition. We further showed that in vivo mechanical stimulation changed the immune system phenotype in young mice toward a more naïve composition. While this rescue was found to be significant in young individuals, aged mice only showed a trend toward the reconstitution of a more naïve immune phenotype. Considering the immune system's experience level in an individual, will likely allow one to differentiate (stratify) and treat (immune-modulate) patients more effectively. This work illustrates the relevance of including immune diagnostics when discussing immunomodulatory therapeutic strategies for the progressively aging population of the industrial countries. |
| first_indexed | 2024-04-12T13:13:05Z |
| format | Article |
| id | doaj.art-94d3e1b6fd3a46ae9a560ced95cf5feb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T13:13:05Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-94d3e1b6fd3a46ae9a560ced95cf5feb2022-12-22T03:31:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00797440180Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and HealingChristian H. Bucher0Christian H. Bucher1Claudia Schlundt2Claudia Schlundt3Dag Wulsten4F. Andrea Sass5F. Andrea Sass6Sebastian Wendler7Sebastian Wendler8Agnes Ellinghaus9Tobias Thiele10Ricarda Seemann11Bettina M. Willie12Hans-Dieter Volk13Hans-Dieter Volk14Georg N. Duda15Georg N. Duda16Georg N. Duda17Katharina Schmidt-Bleek18Katharina Schmidt-Bleek19Julius Wolff Institute and Center for Musculoskeletal Surgery, Charité — Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité — Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité — Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité — Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité — Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité — Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité — Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité — Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité — Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité — Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité — Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité — Universitätsmedizin Berlin, Berlin, GermanyDepartment of Pediatric Surgery, Faculty of Medicine, McGill University, Shriners Hospital for Children, Montreal, QC, CanadaBerlin-Brandenburg Center for Regenerative Therapies, Charité — Universitätsmedizin Berlin, Berlin, GermanyInstitute of Medical Immunology, Charité — Universitätsmedizin Berlin, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité — Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité — Universitätsmedizin Berlin, Berlin, GermanyBerlin Institute of Health Center for Regenerative Therapies, Berlin, GermanyJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité — Universitätsmedizin Berlin, Berlin, GermanyBerlin-Brandenburg Center for Regenerative Therapies, Charité — Universitätsmedizin Berlin, Berlin, GermanyBone formation as well as bone healing capacity is known to be impaired in the elderly. Although bone formation is outpaced by bone resorption in aged individuals, we hereby present a novel path that considerably impacts bone formation and architecture: Bone formation is substantially reduced in aged individual owing to the experience of the adaptive immunity. Thus, immune-aging in addition to chronological aging is a potential risk factor, with an experienced immune system being recognized as more pro-inflammatory. The role of the aging immune system on bone homeostasis and on the bone healing cascade has so far not been considered. Within this study mice at different age and immunological experience were analyzed toward bone properties. Healing was assessed by introducing an osteotomy, immune cells were adoptively transferred to disclose the difference in biological vs. chronological aging. In vitro studies were employed to test the interaction of immune cell products (cytokines) on cells of the musculoskeletal system. In metaphyseal bone, immune-aging affects bone homeostasis by impacting bone formation capacity and thereby influencing mass and microstructure of bone trabeculae leading to an overall reduced mechanical competence as found in bone torsional testing. Furthermore, bone formation is also impacted during bone regeneration in terms of a diminished healing capacity observed in young animals who have an experienced human immune system. We show the impact of an experienced immune system compared to a naïve immune system, demonstrating the substantial differences in the healing capacity and bone homeostasis due to the immune composition. We further showed that in vivo mechanical stimulation changed the immune system phenotype in young mice toward a more naïve composition. While this rescue was found to be significant in young individuals, aged mice only showed a trend toward the reconstitution of a more naïve immune phenotype. Considering the immune system's experience level in an individual, will likely allow one to differentiate (stratify) and treat (immune-modulate) patients more effectively. This work illustrates the relevance of including immune diagnostics when discussing immunomodulatory therapeutic strategies for the progressively aging population of the industrial countries.https://www.frontiersin.org/article/10.3389/fimmu.2019.00797/fullosteoimmunologyregenerationbone healingT cellsadaptive immunityimmune experience |
| spellingShingle | Christian H. Bucher Christian H. Bucher Claudia Schlundt Claudia Schlundt Dag Wulsten F. Andrea Sass F. Andrea Sass Sebastian Wendler Sebastian Wendler Agnes Ellinghaus Tobias Thiele Ricarda Seemann Bettina M. Willie Hans-Dieter Volk Hans-Dieter Volk Georg N. Duda Georg N. Duda Georg N. Duda Katharina Schmidt-Bleek Katharina Schmidt-Bleek Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing Frontiers in Immunology osteoimmunology regeneration bone healing T cells adaptive immunity immune experience |
| title | Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing |
| title_full | Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing |
| title_fullStr | Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing |
| title_full_unstemmed | Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing |
| title_short | Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodeling, and Healing |
| title_sort | experience in the adaptive immunity impacts bone homeostasis remodeling and healing |
| topic | osteoimmunology regeneration bone healing T cells adaptive immunity immune experience |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00797/full |
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