Osteogenesis induced by a bone forming peptide from the prodomain region of BMP-7

Kim, Hyung Keun; Kim, Ji Hyun; Park, Dae Sung; Park, Kyung Soon; Kang, Seong Soo; Lee, Jun Sik; Jeong, Myung Ho; Yoon, Taek Rim

doi:10.1016/j.biomaterials.2012.06.036

Cited by 110 publications

(83 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A dense mineralization was formed in the C2C12 cells treated with BMP2, and this was not observed in the control, which was consistent with the results of previous studies. [44] The cells treated with 25 ng/ml of BMP2 and 4.6 μm Arg-DG conjugate solution significantly increased mineralization in contrast to the cells treated with 25 ng/ml of BMP2 and 5 μm DG or BMP2 alone (Figure 5a). The total calcium content varied between the groups (Figure 5b).…”

Section: Effect Of Arg-dg Conjugate On Mineralizationmentioning

confidence: 91%

Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

Liao

Jung

et al. 2017

Chem Biol Drug Des

View full text Add to dashboard Cite

Water-soluble arginyl-diosgenin (Arg-DG) conjugate was designed, synthesized, and evaluated for a biological activity. The Arg-DG conjugate was characterized using FT-IR, 1 H NMR, 13 C NMR, and HPLC-MS analyses, followed by a biological activity evaluation. Compared with DG, the Arg-DG conjugate showed a decreased cytotoxicity against L929 cells and an increased antiproliferative activity against hepatocellular cells. The safety of the Arg-DG conjugate was confirmed using the highly sensitive Alamar Blue assay, which indicated that it increased the cellular metabolic activity at suitable concentrations. The Arg-DG conjugate promoted an endothelial tube formation as well. Furthermore, the Arg-DG conjugate improved the bone morphogenetic protein 2 (BMP2)-induced osteoblastic differentiation with synergistic effects on alkaline phosphatase (ALP) activity and mineralization. These results suggest that the Arg-DG conjugate developed in this study has great potentials for biomedical applications such as bone tissue engineering. K E Y W O R D SALP assay, arginyl-diosgenin conjugate, bone tissue engineering, cytotoxicity, tube formation assay | INTRODUCTIONDiosgenin [(25R)-spirost-5-en-3ß-ol] (DG) is a major naturally occurring steroid saponin, which is abundantly distributed in the rootstock of yams (Dioscorea sp.) and other plants such as Smilax bockii warb and Trigonella foenum graecum. [1,2] DG has exhibited biological effects in the treatment of various diseases such as hypercholesterolemia, climacteric syndromes including diabetic neuropathy and even cancer. [3][4][5][6] It has also been claimed to have an osteogenic property. DG was reported to inhibit osteoclastogenesis and enhance osteoblastic cell differentiation and the synthesis of cellular bone matrix protein. [7,8] It has been hypothesized that DG could be a potential activator of bone formation and potential therapeutic agent for bone-related diseases including osteoporosis.[8]However, the medical application of DG is considerably limited because of its solubility problem and associated toxicity. The aqueous solubility of DG was determined to be 0.7 ng/ml (1.69 nm).[9] It was also revealed that the low solubility of DG led to poor bioavailability and gastrointestinal mucosal toxicity. [10] As poor solubility has been recognized as a frequently encountered challenge in the field of pharmaceutics, different approaches have been employed to improve the solubility and bioavailability of poorly watersoluble compounds including DG. [11] For instance, an inclusion of complexation of DG and β-cyclodextrin was formed. [12] Iron oxide nanoparticles loaded with DG were prepared. [13] Improving the solubility of DG and decreasing its intrinsic cytotoxicity or at least avoiding any additional toxicity against normal cells are the major challenges to its biomedical application. Numerous efforts have been made to chemically modify this compound to improve its applicable biological activities. Diosgenyl saponin, dioscin analogues were designed to improve its anticancer a...

show abstract

Section: Effect Of Arg-dg Conjugate On Mineralizationmentioning

confidence: 91%

Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

Liao

Jung

et al. 2017

Chem Biol Drug Des

View full text Add to dashboard Cite

show abstract

“…22,37 The second was BMP-7, an important protein involved in several biological processes and able to promote osteogenic differentiation and proliferation during new bone generation. 38 In the control sequence (E7 Poly-G), we added a polyglycine tail to the E7 sequence. All these peptides carried a proline residue at the junction to promote the turn of the sequence away from the surface—as proposed by Gilbert et al 21 Interestingly, the addition of the second domain to the HA-binding domain did not affect its binding properties and no differences were found among the different modular peptides in terms of binding and release profiles.…”

Section: Discussionmentioning

confidence: 99%

Stable biofunctionalization of hydroxyapatite (HA) surfaces by HA-binding/osteogenic modular peptides for inducing osteogenic differentiation of mesenchymal stem cells

et al. 2014

View full text Add to dashboard Cite

Hydroxyapatite (HA), the principal component of bone mineral, shows osteoconductive properties when employed for coating metal implants as well as scaffold materials in synthetic bone grafts. With the goal of providing this material with osteoinductive capabilities to promote faster bone regeneration, we show an easy approach to functionalize HA implant surfaces and enrich them with osteoinductive properties by the use of HA-binding modular peptides. The modular peptides are designed as a combination of two domains, an HA-binding peptide motif and an osteogenic peptide motif derived from the osteogenic growth peptide (OGP) or bone morphometric protein 7 (BMP-7). To identify the best HA-binding peptide, several nature-inspired peptides derived from natural bone extracellular matrix proteins (bone sialoprotein, osteonectin, osteocalcin, and salivarin statherin) were compared for HA-binding activity, revealing concentration-dependent and incubation-time-dependent behaviours. We discovered that a Poly-E heptamer (E7) is the best HA-binding peptide, and thus combined it with a second osteogenic peptidic domain to create an osteoinductive modular peptide. After binding/release characterization, we found that the addition of the second osteogenic peptide domain did not change the binding profile of the modular peptides and caused only a slight change in their release kinetics. Mesenchymal stem cells (MSCs) were cultured on the HA substrates functionalized with modular peptides, and cell adhesion, proliferation, and differentiation in a basal medium (i.e., without any osteogenic supplements) were investigated. Gene expression data clearly showed that MSCs were committed to differentiate into osteoblasts in the presence of the modular peptides. HA discs functionalized with the E7 BMP-7 modular peptide showed the best capability in inducing the osteogenic differentiation of MSCs among all modular peptides studied. The modular peptides can easily be used to functionalize the HA implants through its constituent HA-binding motif, leaving the osteogenic peptide motif protruding from the surface for inducing osteogenesis. Our work opens up a new approach to the formulation of new bioactive HA coatings and implants for bone and dental repair.

show abstract

“…In this case, we chose BFP-1, derived synthetically from BMP-7, and which has bone regenerating efficacy. In particular, our previous in vivo study showed that BFP-1-pretreated multipotent bone marrow stromal stem cell (MBSC)-transplanted animals had strongly increased bone formation compared to BMP-7-pre-treated MBSC-transplanted animals (Kim et al 2012a).…”

Section: Discussionmentioning

confidence: 99%

“…Bone forming peptide-1 (BFP-1) is a peptide derived synthetically from BMP-7. We have previously shown the bone generating efficacy of BFP-1 (Kim et al 2012a).…”

mentioning

confidence: 99%

Clinical application of bone forming peptide-1 for nonunion fracture healing in a dog with Cushing's disease: a case report

Kim¹,

Shim²,

Yoon³

et al. 2015

Vet. Med. - Czech

View full text Add to dashboard Cite

ABSTRACT:A nine-year-old, female Shih Tzu dog was referred to Chonnam National University Veterinary Teaching Hospital with a non-weight bearing lameness, pain in the right forelimb, increased appetite, and dermatological changes. A complete transverse fracture of the right ulnar trochlear notch was detected on survey radiographs. Cushing's disease was diagnosed using the adrenocorticotropic hormone test. The fracture site was repaired using an intramedullary (IM) pin, a 2.0 miniplate and screws, and 1 mg of bone forming peptide-1 (BFP-1) was applied to the fracture site. Post-operative radiographs were performed immediately, and at two and 17 weeks after the first surgery. After the first surgery, the patient fell from the bed, and the IM pin was broken. Thus, a second surgery was performed, and the broken IM pin was removed. To stimulate bone healing, we applied Matrigel containing 3 mg of BFP-1 to the fracture site 20 weeks after the first surgery. A narrowed fracture gap was seen radiographically three weeks after the second surgery, and a hard callus was observed on the cranial fracture line at eight weeks. Bone mineral density at the fracture site increased at 16 weeks. Gradual fracture healing was observed on radiographs over the 35 week period following the second surgery.

show abstract

Osteogenesis induced by a bone forming peptide from the prodomain region of BMP-7

Cited by 110 publications

References 27 publications

Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

Stable biofunctionalization of hydroxyapatite (HA) surfaces by HA-binding/osteogenic modular peptides for inducing osteogenic differentiation of mesenchymal stem cells

Clinical application of bone forming peptide-1 for nonunion fracture healing in a dog with Cushing's disease: a case report

Contact Info

Product

Resources

About