The ternary IGF complex influences postnatal bone acquisition and the skeletal response to intermittent parathyroid hormone

Yakar, Shoshana; Bouxsein, Mary L.; Canalis, Ernesto; Sun, Hui; Glatt, Vaida; Gundberg, Caren; Cohen, Pinchas; Hwang, David; Boisclair, Yves R.; LeRoith, Derek; Rosen, Clifford J.

doi:10.1677/joe.1.06657

Cited by 77 publications

(57 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further evidence for the involvement of IGF-I in PTH-induced anabolism was provided by the observation that 10 week old mice lacking insulin receptor substrate adapting molecule-1, which transmits IGF-I receptor signaling, failed to exhibit an anabolic response to 4 weeks of intermittent PTH administration [90]. Finally, deletion of the IGF-I gene from the liver did not affect PTH-induced anabolism in cancellous bone, suggesting that locally produced IGF-I mediates the response at this site [91]. Interestingly, however, the anabolic response was reduced in cortical bone of these mice suggesting a site specific role of liver-derived IGF-I.…”

Section: Igf-imentioning

confidence: 99%

Molecular and cellular mechanisms of the anabolic effect of intermittent PTH

Jilka

2007

Bone

632

531

View full text Add to dashboard Cite

Intermittent administration of parathyroid hormone (PTH) stimulates bone formation by increasing osteoblast number, but the molecular and cellular mechanisms underlying this effect are not completely understood. In vitro and in vivo studies have shown that PTH directly activates survival signaling in osteoblasts; and that delay of osteoblast apoptosis is a major contributor to the increased osteoblast number, at least in mice. This effect requires Runx2-dependent expression of antiapoptotic genes like Bcl-2. PTH also causes exit of replicating progenitors from the cell cycle by decreasing expression of cyclin D and increasing expression of several cyclin-dependent kinase inhibitors. Exit from the cell cycle may set the stage for pro-differentiating and pro-survival effects of locally produced growth factors and cytokines, the level and/or activity of which are known to be influenced by PTH. Observations from genetically modified mice suggest that the anabolic effect of intermittent PTH requires insulin-like growth factor-I (IGF-I), fibroblast growth factor-2 (FGF-2), and perhaps Wnts. Attenuation of the negative effects of PPARγ may also lead to increased osteoblast number. Daily injections of PTH may add to the pro-differentiating and pro-survival effects of locally produced PTH related protein (PTHrP). As a result, osteoblast number increases beyond that needed to replace the bone removed by osteoclasts during bone remodeling. The pleiotropic effects of intermittent PTH, each of which alone may increase osteoblast number, may explain why this therapy reverses bone loss in most osteoporotic individuals regardless of the underlying pathophysiology.

show abstract

Section: Igf-imentioning

confidence: 99%

Molecular and cellular mechanisms of the anabolic effect of intermittent PTH

Jilka

2007

Bone

632

531

View full text Add to dashboard Cite

show abstract

“…167 Parathyroid hormone regulates the production of IGF-I in bone. 268 Sex steroids regulate the activity of IGF-I. 166 Whereas insulin is present in blood at picomolar concentrations and has a rapid clearance, IGF-I circulates at nanomolar concentrations.…”

Section: Insulin-like Growth Factorsmentioning

confidence: 99%

Growth Factors as Active Participants in Carcinogenesis: A Perspective

Halper

2010

Vet Pathol

View full text Add to dashboard Cite

Growth factors are low molecular peptides active in the stimulation of cell proliferation and in the regulation of embryonic development and cellular differentiation. Significant progress has been made in developing effective strategies to treat human malignancies with new chemical compounds based on a rationale directed against various components of signaling pathways. Many of these drugs target a growth factor receptor-for instance, in the form of monoclonal antibodies or inhibitors of tyrosine kinases, such as monoclonal antibodies against epidermal growth factor receptors used in treating certain types of breast cancer. Imatinib mesylate [Gleevec]) is an excellent example of mediators of signal transduction, such as tyrosine kinases. Growth factors proper are used to ameliorate various and sometimes fatal side effects of cytotoxic and/or myelosuppressive chemotherapy. Basic characteristics of several growth families are discussed with therapeutic modalities based on growth factor activity or, more often, inhibition of such activity.

show abstract

“…The levels of murine IGF-I and IGFBP-3 were measured using mouse-specific in-house enzyme-linked immunoassays (ELISA) that have been developed at UCLA and described previously [25,26]. Murine insulin, leptin, and glucagon levels were assayed using a multiplex ELISA (Linco Research, Inc., St. Louis, MO).…”

Section: Animal Studiesmentioning

confidence: 99%

Carbohydrate restriction, prostate cancer growth, and the insulin‐like growth factor axis

Freedland

Mavropoulos

Wang³

et al. 2007

The Prostate

Self Cite

154

134

View full text Add to dashboard Cite

BACKGROUND. Recent evidence suggests carbohydrate intake may influence prostate cancer biology. We tested whether a no-carbohydrate ketogenic diet (NCKD) would delay prostate cancer growth relative to Western and low-fat diets in a xenograft model. METHODS. Seventy-five male SCID mice were fed a NCKD (84% fat-0% carbohydrate-16% protein kcal), low-fat (12% fat-72% carbohydrate-16% protein kcal), or Western diet (40% fat-44% carbohydrate-16% protein kcal). Low-fat mice were fed ad libitum and the other arms fed via a modified-paired feeding protocol. After 24 days, all mice were injected with LAPC-4 cells and sacrificed when tumors approached 1,000 mm 3 . RESULTS. Despite consuming equal calories, NCKD-fed mice lost weight (up to 15% body weight) relative to low-fat and Western diet-fed mice and required additional kcal to equalize body weight. Fifty-one days after injection, NCKD mice tumor volumes were 33% smaller than Western mice (rank-sum, P ¼ 0.009). There were no differences in tumor volume between low-fat and NCKD mice. Dietary treatment was significantly associated with survival (log-rank, P ¼ 0.006), with the longest survival among the NCKD mice, followed by the low-fat mice. Serum IGFBP-3 was highest and IGF-1:IGFBP-3 ratio was lowest among NCKD mice while serum insulin and IGF-1 levels were highest in Western mice. NCKD mice had significantly decreased hepatic fatty infiltration relative to the other arms.

show abstract

The ternary IGF complex influences postnatal bone acquisition and the skeletal response to intermittent parathyroid hormone

Cited by 77 publications

References 40 publications

Molecular and cellular mechanisms of the anabolic effect of intermittent PTH

Molecular and cellular mechanisms of the anabolic effect of intermittent PTH

Growth Factors as Active Participants in Carcinogenesis: A Perspective

Carbohydrate restriction, prostate cancer growth, and the insulin‐like growth factor axis

Contact Info

Product

Resources

About