Sex differences in systemic bone and muscle loss following femur fracture in mice

Osipov, Benjamin; Paralkar, Manali P.; Emami, Armaun J.; Cunningham, Hailey C.; Tjandra, Priscilla M.; Pathak, Suraj; Langer, Henning T.; Baar, Keith; Christiansen, Blaine A.

doi:10.1002/jor.25116

Cited by 11 publications

(10 citation statements)

References 51 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This difference in lacunar area indicates a distinction between female and male osteocyte function. The mammalian skeleton is a sexually dimorphic organ ( Sharma et al, 2023 ), and female and male bones respond differently to circulating factors, hormones, and myokines as well as other challenges ( Kurapaty and Hsu, 2022 ; Lu et al, 2022 ; Osipov et al, 2022 ). As osteocytes are regulators of bone formation and resorption ( Bonewald, 2011 ; Dallas et al, 2013 ; Robling and Bonewald, 2020 ), this sex difference may be due to differences in male and female osteocytes.…”

Section: Discussionmentioning

confidence: 99%

Deletion of FNDC5/irisin modifies murine osteocyte function in a sex-specific manner

Shimonty,

Pin,

Prideaux

et al. 2024

eLife

View full text Add to dashboard Cite

Irisin, released from exercised muscle, has been shown to have beneficial effects on numerous tissues but its effects on bone are unclear. We found significant sex and genotype differences in bone from wildtype (WT) mice compared to mice lacking Fndc5 (KO), with and without calcium deficiency. Despite their bone being indistinguishable from WT females, KO female mice were partially protected from osteocytic osteolysis and osteoclastic bone resorption when allowed to lactate or when placed on a low-calcium diet. Male KO mice have more but weaker bone compared to WT males, and when challenged with a low-calcium diet lost more bone than WT males. To begin to understand responsible molecular mechanisms, osteocyte transcriptomics was performed. Osteocytes from WT females had greater expression of genes associated with osteocytic osteolysis and osteoclastic bone resorption compared to WT males which had greater expression of genes associated with steroid and fatty acid metabolism. Few differences were observed between female KO and WT osteocytes, but with a low calcium diet, the KO females had lower expression of genes responsible for osteocytic osteolysis and osteoclastic resorption than the WT females. Male KO osteocytes had lower expression of genes associated with steroid and fatty acid metabolism, but higher expression of genes associated with bone resorption compared to male WT. In conclusion, irisin plays a critical role in the development of the male but not the female skeleton and protects male but not female bone from calcium deficiency. We propose irisin ensures the survival of offspring by targeting the osteocyte to provide calcium in lactating females, a novel function for this myokine.

show abstract

Section: Discussionmentioning

confidence: 99%

Deletion of FNDC5/irisin modifies murine osteocyte function in a sex-specific manner

Shimonty,

Pin,

Prideaux

et al. 2024

eLife

View full text Add to dashboard Cite

show abstract

“…We cannot completely rule out the future of bone wasting as a potential comorbid pathology with VML injury because our study only involved animals during their natural developmental stage. First, there is a well-established inflammatory phase associated with VML injury 49,50 that can spill into the systemic vasculature, 51 and systemic inflammation has been linked to bone loss in fracture models 52 and inflammatory diseases. 53,54 Second, our bone-to-muscle ratios were different between VML-injured and uninjured limbs suggesting that the functional capacities of the bone and muscle were not appropriately matched.…”

Section: Discussionmentioning

confidence: 99%

Tibial bone strength is negatively affected by volumetric muscle loss injury to the adjacent muscle in male mice

Schifino

Cooley

Zhong

et al. 2023

Journal Orthopaedic Research

View full text Add to dashboard Cite

This study's objective was to investigate how contractile strength loss associated with a volumetric muscle loss (VML) injury affects the adjacent tibial bone structural and functional properties in male C57BL/6J mice. Mice were randomized into one of two experimental groups: VML‐injured mice that were injured at age 12 weeks and aged to 20 weeks (8 weeks postinjury, VML) and 20‐week‐old age‐matched uninjured mice (Uninjured‐20). Tibial bone strength, mid‐diaphysis cortical geometry, intrinsic material properties, and metaphyseal trabecular bone structure were assessed by three‐point bending and microcomputed tomography (µCT). The plantar flexor muscle group (gastrocnemius, soleus, plantaris) was analyzed for its functional capacities, that is, peak‐isometric torque and peak‐isokinetic power. VML‐injured limbs had 25% less peak‐isometric torque and 31% less peak‐isokinetic power compared to those of Uninjured‐20 mice (p < 0.001). Ultimate load, but not stiffness, was significantly less (10%) in tibias of VML‐injured limbs compared to those from Uninjured‐20 (p = 0.014). µCT analyses showed cortical bone thickness was 6% less in tibias of VML‐injured limbs compared to Uninjured‐20 (p = 0.001). Importantly, tibial bone cross‐section moment of inertia, the primary determinant of bone ultimate load, was 16% smaller in bones of VML‐injured limbs compared to bones from Uninjured‐20 (p = 0.046). Metaphyseal trabecular bone structure was also altered up to 23% in tibias of VML‐injured limbs (p < 0.010). These changes in tibial bone structure and function after a VML injury occur during a natural maturation phase between the age of 12 and 20 weeks, as evidenced by Uninjured‐20 mice having greater tibial bone size and strength compared to uninjured‐aged 12‐week mice.

show abstract

“…This difference in lacunar area indicates a distinction between female and male osteocyte function. The mammalian skeleton is a sexually dimorphic organ Sharma (2023) , and female and male bones respond differently to circulating factors, hormones, and myokines as well as other challenges Kurapaty and Hsu (2022) ; Lu et al (2022) ; Osipov et al (2022) . As osteocytes are regulators of bone formation and resorption Bonewald (2011) ; Dallas et al (2013) ; Robling and Bonewald (2020) , this sex difference may be due to differences in male and female osteocytes.…”

Section: Discussionmentioning

confidence: 99%

Deletion of FNDC5/Irisin modifies murine osteocyte function in a sex-specific manner

Shimonty,

Pin,

Prideaux

et al. 2023

Preprint

View full text Add to dashboard Cite

Irisin, released from exercised muscle, has been shown to have beneficial effects on numerous tissues but its effects on bone are unclear. We found significant sex and genotype differences in bone from wildtype (WT) mice compared to mice lackingFndc5(KO), with and without calcium deficiency. Despite their bone being indistinguishable from WT females, KO female mice were partially protected from osteocytic osteolysis and osteoclastic bone resorption when allowed to lactate or when placed on a low-calcium diet. Male KO mice have more but weaker bone compared to WT males, and when challenged with a low-calcium diet lost more bone than WT males. To begin to understand responsible molecular mechanisms, osteocyte transcriptomics was performed. Osteocytes from WT females had greater expression of genes associated with osteocytic osteolysis and osteoclastic bone resorption compared to WT males which had greater expression of genes associated with steroid and fatty acid metabolism. Few differences were observed between female KO and WT osteocytes, but with a low calcium diet, the KO females had lower expression of genes responsible for osteocytic osteolysis and osteoclastic resorption than the WT females. Male KO osteocytes had lower expression of genes associated with steroid and fatty acid metabolism, but higher expression of genes associated with bone resorption compared to male WT. In conclusion, irisin plays a critical role in the development of the male but not the female skeleton and protects male but not female bone from calcium deficiency. We propose irisin ensures the survival of offspring by targeting the osteocyte to provide calcium in lactating females, a novel function for this myokine.

show abstract

Sex differences in systemic bone and muscle loss following femur fracture in mice

Cited by 11 publications

References 51 publications

Deletion of FNDC5/irisin modifies murine osteocyte function in a sex-specific manner

Deletion of FNDC5/irisin modifies murine osteocyte function in a sex-specific manner

Tibial bone strength is negatively affected by volumetric muscle loss injury to the adjacent muscle in male mice

Deletion of FNDC5/Irisin modifies murine osteocyte function in a sex-specific manner

Contact Info

Product

Resources

About