Table 1 Bone-derived factors mediate glucose/lipid metabolism
From: Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs
Protein | Cell Type | Receptor | Model | Function | Ref. |
|---|---|---|---|---|---|
Ocn | osteoblast | Bone formation | |||
adipocytes | Gprc6a | Ocn−/− mice; in vitro 3T3-L1 adipocytes | Low-dose ucOCN enhances adiponectin expression by cAMP/PAK/Src/ERK/CREB/PPARγ pathway; high-dose ucOCN triggers necroptosis through Fas signaling | ||
white adipose tissue | Gprc6a | ucOCN treated obese mice; 3T3-L1 adipocytes | Upregulate glucose transporter 4 protein and its mRNA (Slc2a4); Increase insulin signaling; downregulate inflammation | ||
brown adipose tissue | Gprc6a | Brown adipocytes (mice DE-2-3 cells and BAT-ADSCs) | Ocn-mediated activation of Gprc6a, futher activate Tcf7 and its downstream target proteins during thermogenesis | ||
liver | Gprc6a | liver-specific GPRC6A knockout (GPRC6ALKO) mice | UcOCN inhibits lipid synthesis and promots lipolysis. | ||
muscles | Gprc6a | Ocn−/−, GPCR6A−/− mice | Exogenous osteocalcin treatmentprevent age-related muscle loss in mice | ||
myofibers | Gprc6a | OcnOsb−/−, Gprc6aMck-/− mice, Ocn−/−, Il6Hsa–/–, Il6rosb–/– mice | Favor uptake and catabolism of glucose and fatty acids; muscle-derived IL-6 sends signal in osteoblasts and osteocalst and futher enhance the rellease of ucOCN in circulation | ||
Fgf23 | Fgf23−/− mice | Growth retardation, hypoglycemic, increased peripheral insulin sensitivity, improved subcutaneous glucose tolerance. | |||
hepatocytes | Fgfr4 | Cultured hepatocytes, Fgfr4−/− mice | Activate Fgfr4, further stimulate PLCγ/calcineurin/NFAT signaling, leading to increased expression and secretion of inflammatory cytokines | ||
Sost | white adipose tissue | Wnt signaling | Sost−/− mice | Active BMP signaling, enhance adipocyte differentiation and metabolism, increase fat mass | |
adipocytes | Sost−/− and SostDmp1 | Block the differentiation of PDGFRα+ adipoprogenitors to mature adipocytes | |||
bone marrow adipose tissue | Wnt signaling | Sost−/− | Regulates the fate determination of bone marrow-adipocyte progenitors by inhibiting the Wnt signaling | ||
adipocytes | Lrp4/5/6 | Lrp4Adipoq and Lrp4Ocn | Lrp4AdipoQ displayed increased glucose and insulin tolerance and reduced serum fatty acids; Lrp4Ocn displayed accumulate body fat and develop impairments in glucose tolerance and insulin sensitivity | ||
beige adipocytes | Wnt signaling | GsαDmp1 | Sclerostin inhibits Wnt signal and activated Ucp1, resulting in beige adippogenesis and less fat mass | ||
Lcn2 | neurons | Mc4r | Lcn2osb−/− mice | Osteoblast-derived Lcn2 maintains glucose homeostasis by inhibiting food intake. | |
beta cells (pancreas) | NA | Col1α1-Lcn2Tg, lcn2 siRNA, db/db | Increase β-cell numbers and functions, improve insulin sensitivity, counteract metabolic dysregulation in obesity. | ||
IL-11 | adipocytes | NA | IL-11−/−, Ocn-Cre; IL-11fl/fl, Adipoq-Cre; IL-11fl/fl | Enhance osteogenesis and bone formation in bone, suppress adipogenesis in adipocyte tissue and increase energy supply | |
Irisin | adpipocytes | NA | Voluntary wheel-running exercise model | Enhance osteogenesis in bone and thermogenesis in adipose tissues | |
Glucocorticoid signaling | adipocytes | NA | Col1α1-Hsd11b2Tg | Control of leptin resistance, obesity and insulin resistance during aging. | |
SLIT2-C | adpipocytes | NA | Shn3−/−, Osx-Cre; Shn3fl/fl, Adipoq-Cre; Shn3fl/fl, Osx-Cre; Slit2fl/fl, Adipoq-Cre; Slit2fl/fl | Control osteogenesis and glucose metabolism. |
