Liver-derived IGF-I regulates cortical bone mass but is dispensable for the osteogenic response to mechanical loading in female mice

Svensson, Johan; Saxon, Leanne; Sjögren, Klara; Koskela, Antti; Tuukkanen, Juha; Ohlsson, Claes

doi:10.1152/ajpendo.00107.2016

Cited by 11 publications

(6 citation statements)

References 47 publications

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“…5 S ), which indicates that MKs/PLTs are an important source of systemic IGF-1 in addition to the liver. Whereas conditional deletion of Igf1 from the liver only affects radial bone growth ( 6 – 8 ), Pf4-Cre; Igf1 f/f mice showed significant defects in both trabecular and cortical bones, suggesting that MKs/PLT-derived IGF-1 promotes osteogenesis in both endocrine and paracrine manners. In contrast to BMSCs, MKs are sparsely distributed throughout the BM space, which could explain why BM adipogenesis is not affected by IGF-1 deficiency in MKs.…”

Section: Discussionmentioning

confidence: 99%

“…Igf1- or Igf1r -deficient mice die perinatally with significantly reduced body size, suggesting that IGF-1 signaling is essential for skeletal development ( 3 , 4 ). Although liver has been considered as the major source of systemic IGF-1 in adulthood ( 5 ), conditional deletion of Igf1 from hepatocytes does not affect linear bone growth or trabecular bone volume, with only minor defects in radial bone growth ( 6 – 8 ). In contrast, conditional deletion of Igf1 from osteoblasts (OBs) or chondrocytes showed severe skeletal defects ( 9 , 10 ), suggesting that locally derived IGF-1 from the bone and cartilage is more important for skeletal development.…”

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confidence: 99%

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Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton

Wang

Zhu

Cao

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Insulin-like growth factor I (IGF-1) is a key regulator of tissue growth and development in response to growth hormone stimulation. In the skeletal system, IGF-1 derived from osteoblasts and chondrocytes are essential for normal bone development; however, whether bone marrow (BM)-resident cells provide distinct sources of IGF-1 in the adult skeleton remains elusive. Here, we show that BM stromal cells (BMSCs) and megakaryocytes/platelets (MKs/PLTs) express the highest levels of IGF-1 in adult long bones. Deletion of Igf1 from BMSCs by Lepr-Cre leads to decreased bone formation, impaired bone regeneration, and increased BM adipogenesis. Importantly, reduction of BMSC-derived IGF-1 contributes to fasting-induced marrow fat accumulation. In contrast, deletion of Igf1 from MKs/PLTs by Pf4-Cre leads to reduced bone formation and regeneration without affecting BM adipogenesis. To our surprise, MKs/PLTs are also an important source of systemic IGF-1. Platelet-rich plasma (PRP) from Pf4-Cre; Igf1 f/f mice showed compromised osteogenic potential both in vivo and in vitro, suggesting that MK/PLT-derived IGF-1 underlies the therapeutic effects of PRP. Taken together, this study identifies BMSCs and MKs/PLTs as two important sources of IGF-1 that coordinate to maintain and regenerate the adult skeleton, highlighting reciprocal regulation between the hematopoietic and skeletal systems.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton

Wang

Zhu

Cao

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Patients with NAFLD was found to have lower IGF-1 levels compared with healthy group, as well as a negative correlation of histological severity of NAFLD and the level of IGF-1 [22] . In mice of 6-and 19month-old, IGF-1 from liver was demonstrated to be needed for maintaining cortical bone mass, furthermore, it was shown that the lack of endocrine IGF-1 caused elevated cortical porosity [23] . While, the main principle of IGF-1 affecting bone structure in NAFLD has not been completely understood.…”

Section: Discussionmentioning

confidence: 99%

Association of TNF-α, IGF-1, and IGFBP-1 levels with the severity of osteopenia in mice with non-alcoholic fatty liver disease

Wang,

Li,

Tian

et al. 2023

Preprint

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Backgrounds: Nonalcoholic fatty liver disease (NAFLD) exhibits a close association with osteoporosis. This work aims to assess the potential effects of NAFLD on the progression of osteopenia in animal models. Methods: Forty-eight C57BL/6 female mice were randomly divided to wild-type (WT) group and high fat diet (HFD) group. The corresponding detections were performed after sacrifice at 16, 24 and 32 weeks, respectively . Results: At 16 weeks, an remarkable increase of body weight and lipid aggregation in the hepatocytes of HFD group was observed compared to the WT group, while the bone structure parameters showed no significant difference. At 24 weeks, the levels of TNF-α and IL-6 in NAFLD mice were significantly increased, while the level of Osteoprotegerin (OPG) mRNA in bone tissue was decreased, and the level of receptor activator of nuclear factor Kappa-B ligand (RANKL) mRNA was increased. Meanwhile, the function of osteoclasts was increased, and the bone microstructure parameters showed significant changes. At 32 weeks, in the HFD mice, the mRNA levels of insulin-like growth factor-1 (IGF-1), Runt-related transcription factor 2 (Runx2), and Osterix (OSX) mRNA were reduced, while the insulin-like growth factor binding protein-1 (IGFBP-1) level was increased. Meanwhile, the osteoblast function was decreased, and the differences in bone structure parameters were more significant, showing obvious osteoporosis. Conclusions: The bone loss in HFD mice is pronounced as NAFLD progresses, and the changes of the TNF-α, IL-6, IGF-1, and IGFBP-1 levels may play critical roles at the different stages of NAFLD in HFD.

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“…Before the mechanical testing, the bones were kept in PBS for 24 h. The biomechanics were analyzed with the three-point bending test (span length 55 mm, loading speed 0.155 mm/min) for the mid tibia using the Instron Universal Testing Machine (Instron 3366; Instron Corp.). The biomechanical parameters were calculated based on the recorded load deformation curves [11].…”

Section: Methodsmentioning

confidence: 99%

Osteoprotective effects of vitamin D(3) in diabetic mice is VDR-mediated and regulated via RANKL/RANK/OPG axis

Labudzynskyi¹,

Shymanskyi²,

Lisakovska³

et al. 2018

Ukr.Biochem.J.

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Liver-derived IGF-I regulates cortical bone mass but is dispensable for the osteogenic response to mechanical loading in female mice

Abstract: Svensson J, Windahl SH, Saxon L, Sjögren K, Koskela A, Tuukkanen J, Ohlsson C. Liver-derived IGF-I regulates cortical bone mass but is dispensable for the osteogenic response to mechanical loading in female mice.

Cited by 11 publications

References 47 publications

Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton

Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton

Association of TNF-α, IGF-1, and IGFBP-1 levels with the severity of osteopenia in mice with non-alcoholic fatty liver disease

Osteoprotective effects of vitamin D(3) in diabetic mice is VDR-mediated and regulated via RANKL/RANK/OPG axis

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