Effects of insulin and insulin‐like growth factor 1 on osteoblast proliferation and differentiation: differential signalling via Akt and ERK

Zhang, Wei; Shen, Xing; Wan, Chao; Zhao, Qiang; Zhang, Lianfang; Zhou, Qi; Deng, Lianfu

doi:10.1002/cbf.2801

Cited by 106 publications

(82 citation statements)

References 20 publications

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“…Higher protein intake is thought to beneficially affect bone health through a number of mechanisms, including its role in maintaining bone structure and increasing insulin‐like growth factor 1 (IGF‐1), an important mediator of osteoblastic activity 1, 2. Conversely, dietary protein is a source of metabolic acid that may lower the pH of urine and increase urinary calcium excretion, which could lower bone mass,3 although a meta‐analyses of randomized trials reported that higher protein intakes are not detrimental to calcium retention or bone mineral loss 4.…”

Section: Introductionmentioning

confidence: 99%

Amino Acid Intakes Are Associated With Bone Mineral Density and Prevalence of Low Bone Mass in Women: Evidence From Discordant Monozygotic Twins

Jennings

Macgregor

Spector

et al. 2015

Journal of Bone and Mineral Research

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Although a higher protein intake, particularly from vegetable sources, has been shown to be associated with higher bone mineral density (BMD) the relative impact of specific amino acids on BMD and risk of osteoporosis remains to be determined. Mechanistic research suggests that a number of specific amino acids, including five nonessential amino acids—alanine, arginine, glutamic acid, glycine, and proline—may play a role in bone health, principally through improved production of insulin and insulin‐like growth factor 1 and the synthesis of collagen and muscle protein. However to date, no previous studies have examined the associations between habitual intake of amino acids and direct measures of BMD and prevalence of osteoporosis or osteopenia, and no studies have examined this relationship in discordant identical twin‐pairs. In these analyses of female monozygotic twin‐pairs discordant for amino acid intake (n = 135), twins with higher intakes of alanine and glycine had significantly higher BMD at the spine than their co‐twins with within‐pair differences in spine‐BMD of 0.012 g/cm2 (SE 0.01; p = 0.039) and 0.014 g/cm2 (SE 0.01; p = 0.026), respectively. Furthermore, in cross‐sectional multivariable analyses of 3160 females aged 18 to 79 years, a higher intake of total protein was significantly associated with higher DXA‐measured BMD at the spine (quartile Q4 to quartile Q1: 0.017 g/cm2, SE 0.01, p = 0.035) and forearm (Q4 to Q1: 0.010 g/cm2, SE 0.003, p = 0.002). Intake of six amino acids (alanine, arginine, glutamic acid, leucine, lysine, and proline) were associated with higher BMD at the spine and forearm with the strongest association observed for leucine (Q4 to Q1: 0.024 g/cm2, SE 0.01, p = 0.007). When intakes were stratified by protein source, vegetable or animal, prevalence of osteoporosis or osteopenia was 13% to 19% lower comparing extreme quartiles of vegetable intake for five amino acids (not glutamic acid or proline). These data provide evidence to suggest that intake of protein and several amino acids, including alanine and glycine, may be beneficial for bone health, independent of genetic background. © 2015 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

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Section: Introductionmentioning

confidence: 99%

Amino Acid Intakes Are Associated With Bone Mineral Density and Prevalence of Low Bone Mass in Women: Evidence From Discordant Monozygotic Twins

Jennings

Macgregor

Spector

et al. 2015

Journal of Bone and Mineral Research

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“…7A, C; P , 0.05). These results suggested that mesenchymal overexpression of NO66 in mice may inhibit the IGF1/IGF1R/Akt signaling pathway, an important signal in the control of chondrocyte and osteoblast proliferation (14,15). Previous in vitro studies reported that NO66 has a histone demethylase activity that is specific for H3K4me3 and H3K36me3.…”

Section: Proliferation Of Skeletal Cells In No66-tg Micementioning

confidence: 84%

“…18). Expression of these factors is differentially regulated by a broad signaling network including IGF1, BMP2, and Wnt/b-catenin signaling pathways (11,(13)(14)(15). To determine changes in mRNA expression of these factors, we performed qPCR assays using total RNA from limbs of E13.5 mouse embryos.…”

Section: Proliferation Of Skeletal Cells In No66-tg Micementioning

confidence: 99%

“…In Osx-null (Osx 2/2 ) mice, expression of bone formation markers, such as type I collagen (Col1), alkaline phosphatase (Alp), bone sialoprotein (Bsp), and Osteocalcin (Oc), was inhibited, and formation of both endochondral and intramembranous bones was abolished (9). Bone formation and growth are also controlled by a broad signaling network including IGF, bone morphogenetic protein (BMP), and members of the Wnt family (11)(12)(13)(14)(15). Previous studies showed that dysregulation of these signaling molecules results in abnormal bone growth (16)(17)(18)(19).…”

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confidence: 99%

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Mesenchyme‐specific overexpression of nucleolar protein 66 in mice inhibits skeletal growth and bone formation

et al. 2015

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Previous studies showed that nucleolar protein 66 (NO66), the Jumonji C-domain-containing histone demethylase for methylated histone H3K4 and H3K36 (H3K36me), negatively regulates osteoblast differentiation in vitro by inhibiting the activity of transcription factor osterix (Osx). However, whether NO66 affects mammalian skeletogenesis in vivo is not yet known. Here, we generated transgenic (TG) mice overexpressing a flag-tagged NO66 transgene driven by the Prx1 (paired related homeobox 1) promoter. We found that NO66 overexpression in Prx1-expressing mesenchymal cells inhibited skeletal growth and bone formation. The inhibitory phenotype was associated with >50% decreases in chondrocyte/osteoblast proliferation and differentiation. Moreover, we found that in bones of NO66-TG mice, expression of Igf1, Igf1 receptor (Igf1r), runt-related transcription factor 2, and Osx was significantly down-regulated (P < 0.05). Consistent with these results, we observed >50% reduction in levels of phosphorylated protein kinase B (Akt) and H3K36me3 in bones of NO66-TG mice, suggesting an inverse correlation between NO66 histone demethylase and the activity of IGF1R/Akt signaling. This correlation was further confirmed by in vitro assays of C2C12 cells with NO66 overexpression. We propose that the decrease in the IGF1R/Akt signaling pathway in mice with mesenchymal overexpression of NO66 may contribute in part to the inhibition of skeletal growth and bone formation.-Chen, Q., Zhang, L., de Crombrugghe, B., Krahe, R. Mesenchyme-specific overexpression of nucleolar protein 66 in mice inhibits skeletal growth and bone formation. FASEB J. 29, 2555-2565 (2015). www.fasebj.org Key Words: histone demethylase • transgenic mice • IGF1R/Akt signaling pathway • osterix THE MAJORITY OF THE MAMMALIAN skeleton is composed of 2 types of tissues: cartilage and bone. Cartilage is made by chondrocytes that are required for the longitudinal growth of bones. Bone forms through 2 distinct processes: intramembranous and endochondral ossification. In intramembranous ossification, bones form directly from the differentiation of mesenchymal progenitor cells, which then differentiate into cells of osteoblast lineage including preosteoblasts, osteoblasts, and osteocytes. However, in endochondral ossification, osteochondroprogenitors, which derive from mesenchymal progenitors, segregate into either chondrocytes that form a cartilage template or osteoblast precursors, which differentiate to form bone tissue that replaces the cartilage template. The progression through mesenchymal condensation, chondrocyte differentiation, and osteogenic-lineage commitment involves 3 key transcription factors: SRY-related HMG-box 9 (Sox9), runt-related transcription factor 2 (Runx2), and osterix (Osx). During endochondral ossification, Sox9 is required for mesenchymal progenitor condensation and expression of type II collagen (Col2) a1 (1-3). Runx2 has a dual role in the regulation of osteogenic-lineage commitment and the differentiation of mature chondrocytes (4-8). R...

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“…Alternatively, downregulation of XRN1 may lead to increased expression of specific miRNAs and/or protein-coding RNAs which then promote the cancerous phenotype. Possible candidates are IGF-1, which is known to induce proliferation of osteoblasts [38][39][40] and/or pro-inflammatory RNAs such as FOS and MYC which are widely known to be involved in cancer progression.…”

Section: Human Diseases Associated With Xrn1mentioning

confidence: 99%

The roles of the exoribonucleases DIS3L2 and XRN1 in human disease

Pashler

Towler

Jones

et al. 2016

Biochemical Society Transactions

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RNA degradation is a vital post-transcriptional process which ensures that transcripts are maintained at the correct level within the cell. DIS3L2 and XRN1 are conserved exoribonucleases which are critical for the degradation of cytoplasmic RNAs. Although the molecular mechanisms of RNA degradation by DIS3L2 and XRN1 have been well studied, less is known about their specific roles in development of multicellular organisms or human disease. This review focusses on the roles of DIS3L2 and XRN1 in the pathogenesis of human disease, particularly in relation to phenotypes seen in model organisms. The known diseases associated with loss of activity of DIS3L2 and XRN1 are discussed, together with possible mechanisms and cellular pathways leading to these disease conditions.

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Effects of insulin and insulin‐like growth factor 1 on osteoblast proliferation and differentiation: differential signalling via Akt and ERK

Cited by 106 publications

References 20 publications

Amino Acid Intakes Are Associated With Bone Mineral Density and Prevalence of Low Bone Mass in Women: Evidence From Discordant Monozygotic Twins

Amino Acid Intakes Are Associated With Bone Mineral Density and Prevalence of Low Bone Mass in Women: Evidence From Discordant Monozygotic Twins

Mesenchyme‐specific overexpression of nucleolar protein 66 in mice inhibits skeletal growth and bone formation

The roles of the exoribonucleases DIS3L2 and XRN1 in human disease

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