Role of the Osteocyte in Musculoskeletal Disease

Shimonty, Anika; Bonewald, Lynda F.; Pin, Fabrizio

doi:10.1007/s11914-023-00788-5

Cited by 8 publications

(1 citation statement)

References 69 publications

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“…Under the physiological calcium-demanding condition of lactation, osteocytes respond to PTHrP by removing their surrounding perilacunar matrix to provide calcium for offspring, and upon weaning this perilacunar matrix is rapidly replaced, a process referred to as perilacunar remodeling ( Qing and Bonewald, 2009 ; Qing et al, 2012 ; Wysolmerski, 2013 ). However, under pathological conditions such as ovariectomy, hyperparathyroidism, hypophosphatemic rickets, and cancer, excessive removal of their perilacunar matrix occurs through osteocytic osteolysis ( Tsourdi et al, 2018 ; Jähn-Rickert and Zimmermann, 2021 ; Pin et al, 2021 ; Shimonty et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

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

Shimonty,

Pin,

Prideaux

et al. 2024

eLife

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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.

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Section: Introductionmentioning

confidence: 99%

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

Shimonty,

Pin,

Prideaux

et al. 2024

eLife

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The role of osteopontin and osteocyte-derived factors in secondary hyperparathyroidism-induced myopathy

Duque,

Crispilho,

Oliveira

et al. 2024

JBMR Plus

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Muscle weakness is a common symptom in chronic kidney disease (CKD) patients, and the pathway by which secondary hyperparathyroidism (SHPT) affects muscle function is unknown. Osteopontin (OPN), a bone matrix protein stimulated by parathyroid hormone (PTH) and phosphate, has been associated with inflammatory muscle diseases. In this observational and prospective cohort study, we evaluated 30 patients with severe SHPT (39 ± 12 years; 18 women), before and 6 months after parathyroidectomy (PTx). We examined the relationships among CKD-MBD parameters; myokine and inflammatory cytokine levels; and changes in resting energy expenditure (REE), muscle function, bone mineral density and muscle-related proteins. At baseline, the patients showed low gene expression of muscle turnover markers and irisin, as well as high protein expression of OPN, transforming growth factor beta (TGF-β), and fibroblast growth factor 21. Six months after PTx, REE and muscle mass had not changed, but physical performance, muscle strength, and bone mass improved, more so in patients undergoing total PTx. Also, there were reductions in the protein expression of OPN (11 vs 3%, P = 0.01) and TGF-β (21 vs 7%, P = 0.002) in muscle, together with a significant increase in irisin muscular levels (30 vs 35 pg/mg, P = 0.02). The gain in bone mass and the increase in irisin levels correlated with a reduction in PTH. The levels of interleukin (IL)-1β, tumor necrosis factor alpha, and IL-17 (markers of myositis) were also lower after PTx. Our data suggests that SHPT plays a role in CKD-induced muscle dysfunction, indirectly, via release of bone-specific proteins, which is partially reverted with PTx.

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

Shimonty,

Pin,

Prideaux

et al. 2023

Preprint

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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

Role of the Osteocyte in Musculoskeletal Disease

Cited by 8 publications

References 69 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

The role of osteopontin and osteocyte-derived factors in secondary hyperparathyroidism-induced myopathy

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

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