Effect of Bone Morphogenetic Protein-2 and Doxycycline on the Differentiation of Osteoprogenitors from Human Femoral Bone

Eglence, Aline; Colterjohn, Nigel; Duivenvoorden, Wilhelmina; Ghert, Michelle; Singh, Gurmit

doi:10.2174/1876525400901010001

Cited by 5 publications

(6 citation statements)

References 33 publications

(47 reference statements)

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“…1 and 2). These results are in agreement with a study that compared the osteogenic potential of BMP2 and doxycycline in human osteoprogenitor cells wherein doxycycline was a stronger inducer of alkaline phosphatase expression 40 . The administration of doxycycline systemically 41 or locally 42 enhances bone regeneration during periodontal surgical procedures.…”

Section: Discussionsupporting

confidence: 90%

Doxycycline Counteracts Bone Morphogenic Protein 2–Induced Osteogenic Mediators

Muthukuru

Sun

2013

Journal of Periodontology

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Combined treatment of BMP2 and doxycycline in PDL cells counteracts the osteogenic mediators. Molecular interaction of growth factors should be explored before using a combination of these biologic molecules. It is important and clinically relevant to determine whether tetracycline and its other derivatives also counteract BMP functions. Animal models should be used to confirm these in vitro results.

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Section: Discussionsupporting

confidence: 90%

Doxycycline Counteracts Bone Morphogenic Protein 2–Induced Osteogenic Mediators

Muthukuru

Sun

2013

Journal of Periodontology

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“…Among these small molecules, the repurposed antibiotic doxycycline (DX) has been linked to promising osteogenic activity that is not related to its antimicrobial action. Low-dose DX exerts osteoinductive actions similar to BMP2 on osteoprogenitor cells, 6 implying DX can be advocated as a valuable small molecular–weight alternative. Although the underlying mechanism has not yet been fully elucidated, reports have suggested that it acts by inhibiting osteoclast formation and inducing osteoclast apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“… 8 Even though low-dose DX is emerging as a promising osteogenic candidate, higher doses have shown deleterious side effects in vitro. 6 , 9 , 10 For instance, unlike lower-dose DX, a 100 µM DX dose exerts cytotoxic actions and negative impacts on the mineralization and differentiation of osteoprecursor cells. 10 …”

Section: Introductionmentioning

confidence: 99%

“…As such, this composite system would limit direct DX contact with cells, eliminate its dose-dependent cytotoxicity, and augment its repurposed osteogenic potential. Although several studies have investigated the osteogenic potential of low-dose DX solution on cells in vitro, 6 , 8 , 9 , 18 the osteogenic action of a composite DX-loaded particulate-delivery system has not yet been addressed. Therefore, in this study, we extrapolated from our previous work establishing the osteogenic potential of hybrid HAp–PCL nanoparticles, 19 in order to osteogenically repurpose DX using a nanocomposite-delivery system.…”

Section: Introductionmentioning

confidence: 99%

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Biomaterial-Based Nanocomposite for Osteogenic Repurposing of Doxycycline

El-Habashy¹,

Eltaher²,

Gaballah³

et al. 2021

IJN

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Background Besides its antimicrobial action, doxycycline (DX) has lately been repurposed as a small-molecule drug for osteogenic purposes. However, osteogenic DX application is impeded by its dose-dependent cytotoxicity. Further, high-dose DX impairs cell differentiation and mineralization. Purpose Integrating DX into a biomaterial-based delivery system that can control its release would not only ameliorate its cytotoxic actions but also augment its osteogenic activity. In this work, we managed to engineer novel composite DX–hydroxyapatite–polycaprolactone nanoparticles (DX/HAp/PCL) to modify DX osteogenic potential. Methods Employing a 2 3 -factorial design, we first optimized HApN for surface-area attributes to maximize DX loading. Composite DX/HAp/PCL were then realized using a simple emulsification technique, characterized using various in vitro methods, and evaluated for in vitro osteogenesis. Results The developed HApN exhibited a favorable crystalline structure, Ca:P elemental ratio (1.67), mesoporous nature, and large surface area. DX/HAp/PCL achieved the highest reported entrapment efficiency (94.77%±1.23%) of DX in PCL-based particles. The developed composite system achieved controlled release of the water-soluble DX over 24 days. Moreover, the novel composite nanosystem managed to significantly ameliorate DX cytotoxicity on bone-marrow stem cells, as well as enhance its overall proliferation potential. Alkaline phosphatase and mineralization assays revealed superior osteodifferentiation potential of the composite system. Quantification of gene expression demonstrated that while DX solution was able to drive bone-marrow stem cells down the osteogenic lineage into immature osteoblasts after 10-day culture, the innovative composite system allowed maturation of osteodifferentiated cells. To the best of our knowledge, this is the first work to elaborate the impact of DX on the expression of osteogenic genes: RUNX2 , OSP, and BSP. Further, the osteogenicity of a DX-loaded particulate-delivery system has not been previously investigated. Conclusion Our findings indicate that repurposing low-dose DX in complementary biomaterial-based nanosystems can offer a prominent osteogenic candidate for bone-regeneration purposes.

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“…Moreover, low concentrations of doxycycline induce an osteoblastic differentiation similar to that obtained from cells exposure to bone morphogenic protein-2 (BMP-2). Doxycycline was also reported to modulate positively osteoprogenitor cells from human femoral cancellous bone (34) . Previous used low doses of orally administered doxycycline for 7 days after molar extraction in Wistar rats.…”

Section: Discussionmentioning

confidence: 96%

Evaluation of Subantimicrobial Dose Doxycycline Effects on Dental Implant Osseointegration in Type II Diabetic Patients

et al. 2018

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Objective: The present study was carried out to compare radiographic outcomes of dental implant in type II diabetic patients with or without adjunctive administration of subantimicrobial dose doxycycline. Subjects and Methods : This study included 20 patients with controlled type II diabetes mellitus of both genders, their age ranged from 40-48years.The study groups were designed in two groups, test group treated with dental implant with systemic administration of subantimicrobial dose doxycycline(SDD) for twice per day for 3 months and control group received dental implant alone. Results: Regarding radiographic marginal bone levels measurements; in both groups the mean marginal bone loss increased by time, with significant difference between both groups where the test group (SDD received group) showed the lower marginal bone loss values. In both groups, bone density measurements increased by time, with significant percentage change recorded for test group (SDD received group) 55.22% while control group recorded 17.40% from base line values. Conclusions: The use of sub-antimicrobial dose doxycycline with dental implants in type II diabetic patients was effective as an adjunctive host modulatory drug. Systemic administration of subantimicrobial dose doxycycline with dental implants in type II diabetic patients resulted in greater increase in bone density and less marginal bone loss thus subantimicrobial dose doxycycline can enhance the osseointegration of dental implants.

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Effect of Bone Morphogenetic Protein-2 and Doxycycline on the Differentiation of Osteoprogenitors from Human Femoral Bone

Cited by 5 publications

References 33 publications

Doxycycline Counteracts Bone Morphogenic Protein 2–Induced Osteogenic Mediators

Doxycycline Counteracts Bone Morphogenic Protein 2–Induced Osteogenic Mediators

Biomaterial-Based Nanocomposite for Osteogenic Repurposing of Doxycycline

Evaluation of Subantimicrobial Dose Doxycycline Effects on Dental Implant Osseointegration in Type II Diabetic Patients

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