ERα Signaling in a Subset of CXCL12‐Abundant Reticular Cells Regulates Trabecular Bone in Mice

• Published in: JBMR plus Vol. 6; no. 8; pp. e10657 - n/a
• Main Authors: Scheffler, Julia M, Gustafsson, Karin L, Barrett, Aidan, Corciulo, Carmen, Drevinge, Christina, Del Carpio Pons, Alicia M, Humeniuk, Piotr, Engdahl, Cecilia, Gustafsson, Jan‐Åke, Ohlsson, Claes, Carlsten, Hans, Lagerquist, Marie K., Islander, Ulrika
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.08.2022; Oxford University Press
• Subjects: Adipocytes; Bone density; Bone growth; Bone loss; Bone marrow; Bone mineral density; Bone remodeling; Bone turnover; Cancellous bone; CCL19 protein; cell; Chemokines; Clonal deletion; Cortical bone; cxcl12; CXCL12 protein; Densitometry; disease; Endocrinology & Metabolism; Endocrinology and Diabetes; Endokrinologi och diabetes; ESTROGEN; Estrogen receptors; estrogen-receptor-alpha; Estrogens; GENETIC ANIMAL MODEL; Homeostasis; Hormone replacement therapy; Immune response; Immune system; lymphocyte; Medicin och hälsovetenskap; Original; Osteoclastogenesis; Osteogenesis; OSTEOIMMUNOLOGY; OSTEOPOROSIS; Osteoprogenitor cells; plasma; recruitment; replacement therapy; Skeleton; stromal; STROMAL CELL; Stromal cells; Vertebrae; United States > US; Germany
• ISSN: 2473-4039; 2473-4039
• DOI: 10.1002/jbm4.10657

ABSTRACT Estrogen has pronounced effects on the immune system, which also influences bone homeostasis. In recent years, stromal cells in lymphoid organs have gained increasing attention as they not only support the regulation of immune responses but also affect bone remodeling. A conditional knockout mouse model where estrogen receptor alpha (ERα) is deleted in CCL19‐expressing stromal cells (Ccl19‐Cre ERαfl/fl mice) was generated and bone densitometry was performed to analyze the importance of stromal cell–specific ERα signaling on the skeleton. Results showed that female Ccl19‐Cre ERαfl/fl mice display reduced total bone mineral density and detailed X‐ray analyses revealed that ERα expression in CCL19‐expressing stromal cells is important for trabecular but not cortical bone homeostasis. Further analysis showed that the trabecular bone loss is caused by increased osteoclastogenesis. Additionally, the bone formation rate was reduced; however, the expression of osteoprogenitor genes was not altered. Analysis of the bone marrow stromal cell compartment revealed a deletion of ERα in a subgroup of CXCL12‐abundant reticular (CAR) cells resulting in increased secretion of the pro‐osteoclastogenic chemokine CXCL12. In conclusion, this study reveals the importance of ERα signaling in CAR cells for bone health. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. Deletion of ERα in CCL19‐expressing stromal cells affects a subpopulation of bone marrow CXCL12‐abundant reticular (CAR) cells. Female Ccl19‐Cre ERαfl/fl mice suffer from: ① increased secretion of CXCL12; ② increased osteoclastogenesis; ③ loss of trabecular bone. Created with BioRender.com.