Bone Morphogenetic Protein-2 Conjugated to Quantum Dot®s is Biologically Functional

Halloran, Daniel; Vrathasha, Vrathasha; Durbano, Hilary W; Nohe, Anja

doi:10.3390/nano10061208

Cited by 10 publications

(9 citation statements)

References 64 publications

(88 reference statements)

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“…Indeed, about 10% of the adult human skeleton is renewed each year and is dependent on the balance between osteoblasts and osteoclasts [ 5 , 8 , 9 , 21 ]. However, as humans age, the balance shifts toward bone resorption, and may lead to bone disorders such as osteopenia and osteoporosis (OP) [ 21 , 22 , 23 , 24 , 25 , 26 ]. Thus, elucidating the precise mechanisms that are responsible for this shift in homeostasis is of the utmost importance.…”

Section: Introductionmentioning

confidence: 99%

Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts

Halloran

Heubel

MacMurray

et al. 2022

JDB

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Proper formation of the skeleton during development is crucial for the mobility of humans and the maintenance of essential organs. The production of bone is regulated by osteoblasts and osteoclasts. An imbalance of these cells can lead to a decrease in bone mineral density, which leads to fractures. While many studies are emerging to understand the role of osteoblasts, less studies are present about the role of osteoclasts. This present study utilized bone marrow cells isolated directly from the bone marrow of femoral heads obtained from osteoarthritic (OA) patients after undergoing hip replacement surgery. Here, we used tartrate resistant acid phosphatase (TRAP) staining, Cathepsin K, and nuclei to identity osteoclasts and their functionality after stimulation with macrophage-colony stimulation factor (M-CSF) and receptor activator of nuclear factor kappa-β ligand (RANKL). Our data demonstrated that isolated cells can be differentiated into functional osteoclasts, as indicated by the 92% and 83% of cells that stained positive for TRAP and Cathepsin K, respectively. Furthermore, isolated cells remain viable and terminally differentiate into osteoclasts when stimulated with RANKL. These data demonstrate that cells isolated from human femoral heads can be differentiated into osteoclasts to study bone disorders during development and adulthood.

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Section: Introductionmentioning

confidence: 99%

Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts

Halloran

Heubel

MacMurray

et al. 2022

JDB

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“…Bone is a composite of collagen fibers reinforced with nano-sized apatites i.e., hydroxyapatite (HA) and whitlockite (WH) [ 1 , 2 ]. Hydroxyapatite is the major component of inorganic phase of bone [ 3 ], has a hexagonal crystalline structure and maintains bone strength. It was previously considered as the best bone alloplast but its poor solubility and fast degradation under the body’s acidic environment has limited its use.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization and Process Optimization of Bone Whitlockite

et al. 2020

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Whitlockite, being the second most abundant bio-mineral in living bone, finds huge applications in tissue regeneration and implants and its synthesis into its pure form has remained a challenge. Although precipitation of whitlockite phase has been reported recently in many publications, effects of various parameters to control such phase as well as conditions for the bulk preparation of this extremely important bio-mineral have not been investigated so far. In this work, we report the precipitation of pure whitlockite phase using common precursors. As reported in the literature, whitlockite is stable in a narrow pH range, therefore; optimization of pH for the stabilization of whitlockite phase has been investigated. Additionally, in order to narrow down the optimum conditions for the whitlockite precipitation, effect of temperature and heating conditions has also been studied. The obtained solids were characterized using powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). From PXRD analysis, it was observed that heating the precursor’s mixture at 100 °C with subsequent aging at the optimized pH resulted in the precipitation of pure whitlockite phase. These results were further confirmed by TGA, SEM and Raman spectroscopy analysis and it was confirmed that the conditions reported here favor whitlockite precipitation without formation of any secondary phase. These reaction conditions were further confirmed by changing all the parameters like aging, heating time, feed rate of precursors one by one. From PXRD analysis of these samples, it was concluded that not only pH but temperature, heating time, aging time and feed rate effect simultaneously on the precipitation of pure whitlockite phase and a subtle change in any of these parameters could lead to the formation of undesired stable secondary calcium phosphate phases.

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“…Therefore, with all these adverse complications, rhBMP-2 may not be suitable as a bone therapeutic. Current research is attempting to develop fluorescent BMP-2 analogs to elucidate the lack of responsiveness to rhBMP-2 [ 249 , 250 ].…”

Section: Clinical Applications and Limitations Of Bmp-2mentioning

confidence: 99%

Bone Morphogenetic Protein-2 in Development and Bone Homeostasis

Halloran

Durbano

Nohe

2020

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Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the Transforming Growth Factor-Beta (TGF-β) superfamily. These proteins are essential to many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Specifically, within the BMP family, Bone Morphogenetic Protein-2 (BMP-2) was the first BMP to be characterized and has been well-studied. BMP-2 has important roles during embryonic development, as well as bone remodeling and homeostasis in adulthood. Some of its specific functions include digit formation and activating osteogenic genes, such as Runt-Related Transcription Factor 2 (RUNX2). Because of its diverse functions and osteogenic potential, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery, tibial shaft repair, and maxillary sinus reconstructive surgery. However, shortly after initial injections of rhBMP-2, several adverse complications were reported, and alternative therapeutics have been developed to limit these side-effects. As the clinical application of BMP-2 is largely implicated in bone, we focus primarily on its role in bone. However, we also describe briefly the role of BMP-2 in development. We then focus on the structure of BMP-2, its activation and regulation signaling pathways, BMP-2 clinical applications, and limitations of using BMP-2 as a therapeutic. Further, this review explores other potential treatments that may be useful in treating bone disorders.

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Bone Morphogenetic Protein-2 Conjugated to Quantum Dot®s is Biologically Functional

Cited by 10 publications

References 64 publications

Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts

Differentiation of Cells Isolated from Human Femoral Heads into Functional Osteoclasts

Synthesis, Characterization and Process Optimization of Bone Whitlockite

Bone Morphogenetic Protein-2 in Development and Bone Homeostasis

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