Lack of CCR3 leads to a skeletal phenotype only in male mice.

Sara Rosendahl, Rima Sulniute, Julia Persson, Sebastian Forsberg, Rebecka Häggvik, Viktor Drewsen, Cecilia Koskinen Holm, Elin Kindstedt, Pernilla Lundberg

Biochemical and biophysical research communications 2022 Sep 10

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We recently showed that adult male mice that lacked the C-C-chemokine receptor 3 (CCR3) exhibited disturbed bone remodeling, which resulted in a cortical bone phenotype of thin femoral cortical bone. However, it remains unknown whether this phenotype would be present during bone modeling, or it affects female mice. Here, we analyzed juvenile and adolescent CCR3-deficient mice to determine when bone modeling was affected in the absence of CCR3 signaling. To investigate whether the CCR3 bone phenotype was sex-related, we analyzed both young female and male mice, and adult females. Micro-computed tomography (μCT) and histomorphometric analyses in adolescent CCR3-deficient male mice revealed reduced cortical bone volume and thickness, and an increase in periosteal mineralization. Interestingly, no skeletal phenotype was observed in adolescent or adult female CCR3-deficient mice. Among juvenile CCR3-deficient mice, neither males nor females showed a skeletal phenotype, which indicated that bone modeling was not affected by the CCR3 deficiency. In summary, adolescent and adult male mice that lacked CCR3 receptors exhibited a cortical phenotype that was not present in female mice, probably due to an estrogen protective mechanism. Based on these and our previous results, we suggest that the importance of CCR3 in cortical bone turnover is related to sex hormones. Because only a few molecules are known to control cortical bone turnover, our novel finding that CCR3 regulated cortical bone thickness only in males suggested that CCR3 is a novel target for controlling cortical bone morphology in male individuals, and perhaps, in post-menopausal women. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Sara Rosendahl, Rima Sulniute, Julia Persson, Sebastian Forsberg, Rebecka Häggvik, Viktor Drewsen, Cecilia Koskinen Holm, Elin Kindstedt, Pernilla Lundberg. Lack of CCR3 leads to a skeletal phenotype only in male mice. Biochemical and biophysical research communications. 2022 Sep 10;620:98-104