Osteocalcin Biomimic Recognizes Bone Hydroxyapatite

Lee, Jae Sam; Tung, Ching–Hsuan

doi:10.1002/cbic.201100162

Cited by 11 publications

(13 citation statements)

References 24 publications

(37 reference statements)

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“…Its Gla residues enable the peptide to bind to CHA but not to other calcium compounds such as calcium oxalate, calcium carbonate, or calcium pyrophosphate. In this study we have used a fluorescein-conjugated peptide (FITC-HABP-19) to visualize CHA in CVC cultures and to monitor calcification in them [6]. …”

Section: Introductionmentioning

confidence: 99%

Effect of Lyso-phosphatidylcholine and Schnurri-3 on Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells to Calcifying Vascular Cells in 3D Culture

Castro-Chavez

Vickers

Lee

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background In vitro cell culture is a widely used technique for investigating a range of processes such as stem cell behavior, regenerative medicine, tissue engineering, and drug discovery. Conventional cell culture is performed in Petri dishes or flasks where cells typically attach to a flat glass or plastic surface as a cell monolayer. However, 2D cell mono-layers do not provide a satisfactory representation of in vivo conditions. A 3D culture could be a much better system for representing the conditions that prevail in vivo. Methods and results To simulate 3D conditions, vascular smooth muscle cells (VSMCs) were loaded with gold–polyvmer–iron oxide hydrogel, enabling levitation of the cells by using spatially varying magnetic fields. These magnetically levitated 3D cultures appeared as freely suspended, clustered cells which proliferated 3–4 times faster than cells in conventional 2D cultures. When the levitated cells were treated with 10 nM lysophosphatidylcholine (LPC), for 3 days, cell clusters exhibited translucent extensions/rods 60–80 µm wide and 200–250 µm long. When 0.5 µg/µl Schnurri-3 was added to the culture containing LPC, these extensions were smaller or absent. When excited with 590–650 nm light, these extensions emitted intrinsic fluorescence at >667 nm. When the 3D cultures were treated with a fluorescent probe specific for calcium hydroxyapatite (FITC-HABP-19), the cell extensions/rods emitted intensely at 518 nm, the λmax for FITC emission. Pellets of cells treated with LPC were more enriched in calcium, phosphate, and glycosaminogly-cans than cells treated with LPC and Schnurri-3. Conclusions In 3D cultures, VSMCs grow more rapidly and form larger calcification clusters than cells in 2D cultures. Transdifferentiation of VSMC into calcifying vascular cells is enhanced by LPC and attenuated by Schnurri-3. General significance The formation of calcified structures in 3D VSMC cultures suggests that similar structures may be formed in vivo.

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Section: Introductionmentioning

confidence: 99%

Effect of Lyso-phosphatidylcholine and Schnurri-3 on Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells to Calcifying Vascular Cells in 3D Culture

Castro-Chavez

Vickers

Lee

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…FITC-labeled HABP-19 and the corresponding FITC-labeled control cHABP probes were prepared as previously described [27]. The sequences of HABP-19 and control cHABP are FITC-βAγEPRRγEVAγELγEPRRγEVAγEL-NH 2 and FITC-βAEPRREVAELEPRREVAEL-NH 2 , respectively.…”

Section: Methodsmentioning

confidence: 99%

“…However, HA calcifications can be found in both benign and malignant lesions, although they are most often seen in proliferative lesions, including carcinoma [24–26]. Recently, we have developed a HA binding peptide (HABP-19) inspired from protein OCN that was used as a targeting imaging contrast for HA calcification in cardiovascular diseases and early osteoblastic activity [23,27]. In the present work we have used HABP-19 molecular imaging agent to validate HA calcification in osteotropic tumors (ex vivo) and human SaOS-2 cells (in vitro).…”

Section: Introductionmentioning

confidence: 99%

Osteotropic cancer diagnosis by an osteocalcin inspired molecular imaging mimetic

Lee

Tung

2013

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Although microcalcifications of hydroxyapatite can be found in both benign and malignant osteotropic tumors, they are mostly seen in proliferative lesions, including carcinoma. The aim of this present study is to develop a molecular imaging contrast agent for selective identification of hydroxyapatite calcification in human osteotropic tumor tissues ex vivo and in human osteosarcoma cells in vitro. Methods A bioinspired biomarker, hydroxyapatite binding peptide (HABP), was designed to mimic natural protein osteocalcin property in vivo. A fluorescein isothiocyanate dye conjugated HABP (HABP-19) was utilized to characterize hydroxyapatite on human osteotropic tumor tissue sections ex vivo and to selectively image hydroxyapatite calcifications in human osteosarcoma cells in vitro. Results Using a HABP-19 molecular imaging probe, we have shown that it is possible to selectively image hydroxyapatite calcifications in osteotropic cancers ex vivo and in human SaOS-2 osteosarcoma cells in vitro. Conclusion Hydroxyapatite calcifications were selectively detected in osteotropic tissues ex vivo and in the early stage of the calcification process of SaOS-2 human osteosarcoma in vitro using our HABP-19 molecular imaging probe. This new target-selective molecular imaging probe makes it possible to study the earliest events associated with hydroxyapatite deposition in various osteotropic cancers at the cellular and molecular levels. General significance It potentially could be used to diagnose and treat osteotropic cancer or to anchor therapeutic agents directing the local distribution of desired therapy at calcified sites.

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“…15 Previously a 19-mer peptide, called HABP-19, that incorporated six residues of Gla was developed by us and showed excellent properties as a bone imaging probe both in vitro and in vivo. 9 In that study, it was found that the peptide lost its affinity to HA if the unusual bidentate Gla residues were replaced by normal Glutamate (Glu) residues (Figure 1), which have only one carboxyl group on the side chain, suggesting the critical role of the bidentate structure. An iminodiacetate (IDA) group (Figure 1), which imitates the bidentate structure of dicarboxylate group on the Gla side chain, has been explored for bone binding.…”

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confidence: 94%

Bidentate iminodiacetate modified dendrimer for bone imaging

Pes

Kim

Tung

2017

Bioorganic & Medicinal Chemistry Letters

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A new dendrimer probe was designed for bone imaging. Bidentate iminodiacetate groups were introduced to the probe to obtain strong bind to bones. The assembled dendrimeric probe, with four iminodiacetate moieties and a fluorescent tag, displayed good selectivity to hydroxyapatite, calcium oxalate and calcium phosphate salts. In mice, the probe offered vivid skeletal details after intravenous delivery.

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Osteocalcin Biomimic Recognizes Bone Hydroxyapatite

Cited by 11 publications

References 24 publications

Effect of Lyso-phosphatidylcholine and Schnurri-3 on Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells to Calcifying Vascular Cells in 3D Culture

Effect of Lyso-phosphatidylcholine and Schnurri-3 on Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells to Calcifying Vascular Cells in 3D Culture

Osteotropic cancer diagnosis by an osteocalcin inspired molecular imaging mimetic

Bidentate iminodiacetate modified dendrimer for bone imaging

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