Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner – A quantitative in vitro gene expression analysis of Dlx5, Runx2, OCN, MSX1 and MSX2

Koch, Felix P.; Merkel, Christina; Al‐Nawas, Bilal; Smeets, Ralf; Ziebart, Thomas; Wagner, Wilfried

doi:10.1016/j.jcms.2010.10.007

Cited by 37 publications

(23 citation statements)

References 49 publications

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“…In agreement with our results, Ponader et al found a positive differentiation stimulus on osteoblast differentiation with quantification of alkaline phosphatase and OCN gene expression [41]. Koch et al found that Zol at high concentrations enhanced the gene expression of OCN, whereas lower concentrations led to decreased gene expression [42].…”

Section: Discussionsupporting

confidence: 93%

Controlled Delivery of Zoledronate Improved Bone Formation Locally In Vivo

et al. 2014

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Bisphosphonates (BPs) have been widely used in clinical treatment of bone diseases with increased bone resorption because of their strong affinity for bone and their inhibition of bone resorption. Recently, there has been growing interest in their improvement of bone formation. However, the effect of local controlled delivery of BPs is unclear. We used polylactide acid-glycolic acid copolymer (PLGA) as a drug carrier to deliver various doses of the bisphosphonate zoledronate (Zol) into the distal femur of 8-week-old Sprague-Dawley rats. After 6 weeks, samples were harvested and analyzed by micro-CT and histology. The average bone mineral density and mineralized bone volume fraction were higher with medium- and high-dose PLGA-Zol (30 and 300 µg Zol, respectively) than control and low-dose Zol (3 µg PLGA-Zol; p<0.05). Local controlled delivery of Zol decreased the numbers of osteoclast and increased the numbers of osteoblast. Moreover, local controlled delivery of medium- and high-dose Zol accelerated the expression of bone-formation markers. PLGA used as a drug carrier for controlled delivery of Zol may promote local bone formation.

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Section: Discussionsupporting

confidence: 93%

Controlled Delivery of Zoledronate Improved Bone Formation Locally In Vivo

et al. 2014

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“…Our investigation, focusing particularly on the ex vivo effects at the molecular and cellular level of ZA treatment, supports its anabolic effects on osteogenic precursors, previously demonstrated in vitro [27] and in a sickle cell disease mouse model [28]. …”

Section: Discussionsupporting

confidence: 83%

Enhanced Osteogenic Differentiation in Zoledronate-Treated Osteoporotic Patients

Carbonare

Mottes

Malerba

et al. 2017

IJMS

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Bisphosphonates are well known inhibitors of osteoclast activity and thus may be employed to influence osteoblast activity. The present study was designed to evaluate the in vivo effects of zoledronic acid (ZA) on the proliferation and osteoblastic commitment of mesenchymal stem cells (MSC) in osteoporotic patients. We studied 22 postmenopausal osteoporotic patients. Densitometric, biochemical, cellular and molecular data were collected before as well as after 6 and 12 months of ZA treatment. Peripheral blood MSC-like cells were quantified by colony-forming unit fibroblastic assay; their osteogenic differentiation potential was evaluated after 3 and 7 days of induction, respectively. Circulating MSCs showed significantly increased expression levels of osteoblastic marker genes such as Runt-related transcription factor 2 (RUNX2), and Osteonectin (SPARC) during the 12 months of monitoring time. Lumbar bone mineral density (BMD) variation and SPARC gene expression correlated positively. Bone turnover marker levels were significantly lowered after ZA treatment; the effect was more pronounced for C terminal telopeptide (CTX) than for Procollagen Type 1 N-Terminal Propeptide (P1NP) and bone alkaline phosphatase (bALP). Our findings suggest a discrete anabolic activity supported by osteogenic commitment of MSCs, consequent to ZA treatment. We confirm its anabolic effects in vivo on osteogenic precursors.

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“…These data indirectly suggested a preferential commitment of progenitor cells to differentiate into osteoblasts instead of adipocytes 27. Previous in vitro studies have shown that other bisphosphonates (i.e., zoledronate, ibandronate, and clodronate) increased the expression of osteogenic genes, including distal-less homeobox 5 (dlx5), RUNX2, the homeobox analogs known as melanocyte-stimulating hormone (MSH) homeobox 1 and 2 (msx1 and msx2), and OCN 28. Taken together, these data agree with our results showing a significant increase in the bone expression of RUNX2, a key transcription factor for osteoblast differentiation, in cirrhotic mice treated with pamidronate.…”

Section: Discussionmentioning

confidence: 83%

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

Spirlandeli¹,

Dick-de-Paula²,

Zamarioli³

et al. 2017

Clinics

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OBJECTIVES:The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated.METHODS:The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression.RESULTS:CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice.CONCLUSION:Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

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Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner – A quantitative in vitro gene expression analysis of Dlx5, Runx2, OCN, MSX1 and MSX2

Cited by 37 publications

References 49 publications

Controlled Delivery of Zoledronate Improved Bone Formation Locally In Vivo

Controlled Delivery of Zoledronate Improved Bone Formation Locally In Vivo

Enhanced Osteogenic Differentiation in Zoledronate-Treated Osteoporotic Patients

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

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