Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions*

Rajaram, Sujatha; Baylink, David J.; Mohan, Subburaman

doi:10.1210/edrv.18.6.0321

Cited by 543 publications

(511 citation statements)

References 320 publications

(314 reference statements)

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“…The frizzledrelated protein, Fzb, modulates Wnt-␤-catenin signaling, important for bone formation (22). IGFBP-5 is related to osteoblast proliferation and differentiation, both dependently on and independently of IGF-1 action (23). OASIS, a member of the CREB/ATF transcription factor family with a transmembrane domain, is highly expressed in osteoblasts (24) and undergoes regulated intramembrane proteolysis in response to endoplasmic reticulum stress inducing Col1a1 gene transcription (25).…”

Section: Discussionmentioning

confidence: 99%

Parathyroid Hormone-responsive Smad3-related Factor, Tmem119, Promotes Osteoblast Differentiation and Interacts with the Bone Morphogenetic Protein-Runx2 Pathway

Hisa

Inoue

Hendy

et al. 2011

Journal of Biological Chemistry

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The mechanisms whereby the parathyroid hormone (PTH) exerts its anabolic action on bone are incompletely understood. We previously showed that inhibition of ERK1/2 enhanced Smad3-induced bone anabolic action in osteoblasts. These findings suggested the hypothesis that changes in gene expression associated with the altered Smad3-induced signaling brought about by an ERK1/2 inhibitor would identify novel bone anabolic factors in osteoblasts. We therefore performed a comparative DNA microarray analysis between empty vector-transfected mouse osteoblastic MC3T3-E1 cells and PD98059-treated stable Smad3-overexpressing MC3T3-E1 cells. Among the novel factors, Tmem119 was selected on the basis of its rapid induction by PTH independent of later increases in endogenous TGF-␤. The levels of Tmem119 increased with time in cultures of MC3T3-E1 cells and mouse mesenchymal ST-2 cells committed to the osteoblast lineage by BMP-2. PTH stimulated Tmem119 levels within 1 h as determined by Western blot analysis and immunocytochemistry in MC3T3-E1 cells. MC3T3-E1 cells stably overexpressing Tmem119 exhibited elevated levels of Runx2, osteocalcin, alkaline phosphatase, and ␤-catenin, whereas Tmem119 augmented BMP-2-induced Runx2 levels in mesenchymal cells. Tmem119 interacted with Runx2, Smad1, and Smad5 in C2C12 cells. In conclusion, we identified a Smad3-related factor, Tmem119, that is induced by PTH and promotes differentiation in mouse osteoblastic cells. Tmem119 is an important molecule in the pathway downstream of PTH and Smad3 signaling in osteoblasts.Bone remodeling is controlled by bone resorption and subsequent osteoblastic bone formation. Insights into the mechanisms of osteoclastic bone resorption have led to the development of reagents that potently suppress bone resorption for the treatment of osteoporosis. On the other hand, the impairment of osteoblastic bone formation is considered to be the main driving force in age-related, glucocorticoid-induced, and diabetes-related osteoporosis. However, many aspects of osteoblastic bone formation remain to be understood. Intermittent parathyroid hormone (PTH) 3 is one of the most potent anabolic agents; it stimulates de novo osteoblastic bone formation and is superior to bisphosphonates in the treatment of osteoporosis (1, 2). The anabolic action of PTH is exerted partly through local growth factors and transcriptional regulators as well by as an anti-apoptotic action in osteoblasts (3, 4). However, the precise mechanisms by which PTH exerts its anabolic action on bone are incompletely understood.We showed previously that Smad3, a crucial TGF-␤-signaling molecule, promotes alkaline phosphatase (ALP) activity in mouse osteoblastic MC3T3-E1 cells (5, 6), and Borton et al. (7) have found that mice with targeted disruption of Smad3 exhibit osteopenia caused by decreased bone formation, suggesting that the Smad3 molecule is a promoter of bone formation. Moreover, we demonstrated that TGF-␤-responsive ERK1/2 and c-Jun N-terminal kinase (JNK) cascades negatively regulate Smad3-ind...

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Section: Discussionmentioning

confidence: 99%

Parathyroid Hormone-responsive Smad3-related Factor, Tmem119, Promotes Osteoblast Differentiation and Interacts with the Bone Morphogenetic Protein-Runx2 Pathway

Hisa

Inoue

Hendy

et al. 2011

Journal of Biological Chemistry

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“…Fur- WISP3 REGULATION OF COLLAGEN AND AGGRECANthermore, specific binding of IGFs to the CCN-family protein CTGF has also been documented (33). Accordingly, it is possible that WISP3 tethers IGF-1 to the IGF-1 receptor by competing with antagonistic IGFBPs (34,35) (Figure 5). If this is the case, the stimulation of the IGF-1 receptor tyrosine kinase by WISP3 may contribute to the activation of SOX transcription factors and subsequent up-regulation of chondrocyte-specific gene expression, via a MAP kinase signaling cascade, as has been reported (36).…”

Section: Discussionmentioning

confidence: 99%

WISP3‐dependent regulation of type II collagen and aggrecan production in chondrocytes

Sen¹,

Cheng²,

Goldring³

et al. 2004

Arthritis & Rheumatism

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Objective. WISP3 (Wnt-1-inducible secreted protein 3) is a member of the CCN (connective tissue growth factor, cysteine-rich 61, nephroblastoma overexpressed) family of connective tissue growth factors. WISP3 mutations have been linked to progressive pseudorheumatoid dysplasia (PPRD). The present study was conducted to investigate whether WISP3 is responsible for the expression of cartilage-specific molecules.Methods. WISP3 expression in human cartilage was assessed by immunostaining with anti-WISP3 antibody. The effect of WISP3 on chondrocyte-specific gene regulation was determined by transfecting human chondrocyte lines C-28/I2 and T/C-28a2 with a WISP3 expression vector. Alterations in WISP3-mediated messenger RNA and protein expression of cartilage-specific molecules were assessed by reverse transcriptasepolymerase chain reaction and immunoblotting.Results. Immunohistochemistry experiments demonstrated that WISP3 protein is expressed in the midzone chondrocytes of normal adult articular cartilage, in chondrocyte clusters of osteoarthritic cartilage, and in the zone of proliferating chondrocytes of fetal growth cartilage. Human chondrocyte lines C-28/I2 and T/C-28a2 transfected with a WISP3 expression vector produced increased amounts of the cartilage-specific matrix molecules type II collagen and aggrecan, in part via activation of the sex-determining region Y-type high mobility group box (SOX) family of transcription factors. In contrast, a mutant WISP3, previously found to be associated with PPRD, had impaired effects on cartilage-specific gene expression.Conclusion. Our experimental results suggest that WISP3 supports cartilage integrity by regulating the expression of type II collagen and aggrecan, and mutations linked with PPRD can compromise this function and produce cartilage loss.

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“…6 In blood circulation, over 75% of IGF-I is bound to the insulin-like binding protein (IGFBP)-3. 7 Circulating IGF-I levels are largely determined by genetic factors and age, 8,9 and are also affected by sex, anthropometric indices, physical activity, exogenous sex hormones, smoking, alcohol consumption 10 and nutritional status. 6 Circulating levels of IGF-I and IGFBP-3 concentrations vary considerably between normal individuals, but blood levels in each individual are relatively constant.…”

Section: Introductionmentioning

confidence: 99%

Body mass index, waist circumference and waist–hip ratio and serum levels of IGF-I and IGFBP-3 in European women

et al. 2006

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Objective: To examine the relationship between body mass index (BMI) and waist-hip ratio (WHR) with serum levels of insulinlike growth factor-I (IGF-I), and its binding protein (IGFBP)-3. Design: Cross-sectional study on 2139 women participating in a case-control study on breast cancer and endogenous hormones. Data on lifestyle and reproductive factors were collected by means of questionnaires. Body height, weight, waist and hip circumferences were measured. Serum levels of IGF-I and insulin-like binding protein (IGFBP)-3 were measured by enzymelinked immunosorbent assays. Adjusted mean levels of IGF-I and IGFBP-3 across quintiles of BMI, waist circumference, and WHR were calculated by linear regression. Results were adjusted for potential confounders associated with IGF-I and IGFBP-3. Results: Adjusted mean serum IGF-I values were lower in women with BMIo22.5 kg/m 2 or BMI429.2 kg/m 2 compared to women with BMI within this range (P heterogeneity o0.0001, P trend ¼ 0.35). Insulin-like growth factor-I was not related to WHR after adjustment for BMI. IGF-binding protein-3 was linearly positively related to waist and WHR after mutual adjustment. The molar ratio IGF-I/IGFBP-3 had a non-linear relation with BMI and a linear inverse relationship with WHR (P trend ¼ 0.005). Conclusions: Our data confirm the nonlinear relationship of circulating IGF-I to total adiposity in women. Serum IGFBP-3 was positively related to central adiposity. These suggest that bioavailable IGF-I levels could be lower in obese compared to nonobese women and inversely related to central adiposity.

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Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions*

Cited by 543 publications

References 320 publications

Parathyroid Hormone-responsive Smad3-related Factor, Tmem119, Promotes Osteoblast Differentiation and Interacts with the Bone Morphogenetic Protein-Runx2 Pathway

Parathyroid Hormone-responsive Smad3-related Factor, Tmem119, Promotes Osteoblast Differentiation and Interacts with the Bone Morphogenetic Protein-Runx2 Pathway

WISP3‐dependent regulation of type II collagen and aggrecan production in chondrocytes

Body mass index, waist circumference and waist–hip ratio and serum levels of IGF-I and IGFBP-3 in European women

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