Anabolic actions of PTH (1-34): Use of a novel tissue engineering model to investigate temporal effects on bone

Pettway, Glenda J.; Schneider, Abraham; Koh, Amy J.; Widjaja, Effendi; Morris, Michael D.; Meganck, Jeffrey A.; Goldstein, Steven A.; McCauley, Laurie K.

doi:10.1016/j.bone.2005.02.015

Cited by 77 publications

(84 citation statements)

References 44 publications

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“…OCN was significantly increased in PTH-treated implants with treatment initiated 1 week after implanting cells and decreased in later treatment groups, confirming that the implanted BMSCs in each group were at different stages of differentiation when PTH treatment was initiated. This is further supported by data from a previous study where early events of PTH action in 1 week and 2 week old BMSC implants were evaluated [15]. OCN mRNA was low in 1 week old ossicles and increased significantly at 2 weeks, confirming that PTH targets cells at the stage of transition from pre-osteoblasts to mature matrix producing osteoblasts.…”

Section: Discussionsupporting

confidence: 79%

“…BMSCs were isolated from the femoral, tibial, and humeral cavities of 4-to 8-week old C57BL/ 6 mice, and mice expressing luciferase (B6; C3-Tg (TettTALuc) 1Dgs/J, Jackson Laboratory, Bar Harbor, ME) as previously described [15]. The luciferase transgenic mice contain modified tetracycline controlled transactivator (tTA) and luciferase genes under the control of tetracycline-responsive promoter elements (TREs) and widely express luciferase in the absence of tetracycline [16].…”

Section: Ectopic Ossicle Modelmentioning

confidence: 99%

“…Histograms were then generated to select a global mineralized tissue threshold that delineated bone from all other tissues. The bone mineral content (BMC) and tissue mineral content (TMC) were calculated on the microCT images (MicroView v2, Advanced Bone Application, GE Healthcare) [20], and these data were used in conjunction with a custom MATLAB algorithm to calculate the bone mineral density (BMD), tissue mineral density (TMD) and bone volume fraction (BVF) as previously described [15]. Daily scanning procedures included the use of a phantom for system calibration.…”

Section: Microctmentioning

confidence: 99%

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Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation

Pettway

Meganck

Koh

et al. 2008

Bone

107

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PTH (1-34) is the only FDA-approved anabolic agent for osteoporosis treatment in the U.S., but its mechanisms are not completely understood. This study investigated PTH effects on osteogenic cells at various stages of differentiation and proliferation using an engineered bone growth model in vivo. Ossicles were generated from bone marrow stromal cells (BMSCs) implanted in immunocompromised mice. Three weeks of PTH (40μg/kg/d) or vehicle treatment initiated 1 day, 1, 2, or 3wks after BMSC implantation resulted in an anabolic response in PTH-treated implants (via histomorphometry and microCT) in all treatment groups. A novel in vivo tracking strategy with luciferase tagged BMSCs and weekly bioluminescent imaging of ossicles revealed increased donor cell proliferation in PTH-treated ossicles. The greatest increase occurred during the first week, and the activity remained elevated in PTH-treated implants over time. Zoledronic acid (ZA) was combined with PTH to delineate interactive mechanisms of these bone active agents. Combining ZA with PTH treatment reduced the PTH-mediated increase in luciferase BMSC activity, serum osteocalcin, and serum tartrate resistant acid phosphotase-5b (TRAP-5b) but ZA did not reduce the PTH-induced increase in total bone. Since zoledronic acid reduced PTH-induced proliferation without reducing bone volume, these data suggests that combining PTH and bisphosphonate therapy warrants further investigation in the treatment of bone disorders.

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Section: Discussionsupporting

confidence: 79%

Section: Ectopic Ossicle Modelmentioning

confidence: 99%

Section: Microctmentioning

confidence: 99%

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Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation

Pettway

Meganck

Koh

et al. 2008

Bone

107

View full text Add to dashboard Cite

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“…Consistent with a PTH-induced increase in the number of differentiating osteoblast progenitors, marrow cell cultures established from young ovariectomized rats receiving intermittent PTH exhibited an increased ability to form a mineralized matrix compared to vehicle controls [67]. Moreover, intermittent PTH accelerated the development of ossicles formed by murine bone marrowderived osteoblast progenitors following transplantation into immunocompromised mice [68].…”

Section: Effects Of Intermittent Pth On the Replication And Differentmentioning

confidence: 71%

Molecular and cellular mechanisms of the anabolic effect of intermittent PTH

Jilka

2007

Bone

630

531

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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.

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“…Raman spectroscopy can be used to monitor effects on bone mineral and matrix quality. Even before the development of noninvasive techniques, Raman spectroscopy was used to follow temporal-dependent effects of PHT on mineralization [59]. Only mineral-to-matrix ratio was reported, and other measures of bone quality such as crystallinity and carbonate-to-phosphate ratio and collagen quality data have not been reported.…”

Section: Age-related Changes In Bonementioning

confidence: 99%

Raman Assessment of Bone Quality

Morris

Mandair

2011

Clinical Orthopaedics &Amp; Related Research

448

477

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Background Progress in the diagnosis and prediction of fragility fractures depends on improvements to the understating of the compositional contributors of bone quality to mechanical competence. Raman spectroscopy has been used to evaluate alterations to bone composition associated with aging, disease, or injury. Questions/purposes In this survey we will (1) review the use of Raman-based compositional measures of bone quality, including mineral-to-matrix ratio, carbonateto-phosphate ratio, collagen quality, and crystallinity; (2) review literature correlating Raman spectra with biomechanical and other physiochemical measurements and with bone health; and (3) discuss prospects for ex vivo and in vivo human subject measurements. Methods ISI Web of Science was searched for references to bone Raman spectroscopy in peer-reviewed journals. Papers from other topics have been excluded from this review, including those on pharmaceutical topics, dental tissue, tissue engineering, stem cells, and implant integration. Results Raman spectra have been reported for human and animal bone as a function of age, biomechanical status, pathology, and other quality parameters. Current literature supports the use of mineral-to-matrix ratio, carbonate-tophosphate ratio, and mineral crystallinity as measures of bone quality. Discrepancies between reports arise from the use of band intensity ratios rather than true composition ratios, primarily as a result of differing collagen band selections. Conclusions Raman spectroscopy shows promise for evaluating the compositional contributors of bone quality in ex vivo specimens, although further validation is still needed. Methodology for noninvasive in vivo assessments is still under development.

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Anabolic actions of PTH (1-34): Use of a novel tissue engineering model to investigate temporal effects on bone

Cited by 77 publications

References 44 publications

Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation

Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation

Molecular and cellular mechanisms of the anabolic effect of intermittent PTH

Raman Assessment of Bone Quality

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