2. Academic Validation
  3. Glycinamide Facilitates Nanocomplex Formation and Functions Synergistically with Bone Morphogenetic Protein 2 to Promote Osteoblast Differentiation In Vitro and Bone Regeneration in a Mouse Calvarial Defect Model

Glycinamide Facilitates Nanocomplex Formation and Functions Synergistically with Bone Morphogenetic Protein 2 to Promote Osteoblast Differentiation In Vitro and Bone Regeneration in a Mouse Calvarial Defect Model

  • Tissue Eng Regen Med. 2024 Oct;21(7):1093-1107. doi: 10.1007/s13770-024-00657-x.
Sang-Hyeon Nam # 1,  Ju Ang Kim # 1,  Soomin Lim 1,  Su Jeong Lee 1,  Chun-Ho Kim 2,  Jong-Sup Bae 3,  Yong Chool Boo 4,  Young-Jin Kim 5,  Eui Kyun Park 6
Affiliations

Affiliations

  • 1 Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Bio-Tooth Regeneration, Kyungpook National University, Daegu, 41940, Republic of Korea.
  • 2 Laboratory of Tissue Engineering, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea.
  • 3 College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea.
  • 4 Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.
  • 5 Department of Biomedical Engineering, Daegu Catholic University, Gyeongsan, 38430, Republic of Korea. yjkim@cu.ac.kr.
  • 6 Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Bio-Tooth Regeneration, Kyungpook National University, Daegu, 41940, Republic of Korea. epark@knu.ac.kr.
  • # Contributed equally.
PMID: 38955905 DOI: 10.1007/s13770-024-00657-x
Abstract

Background: This study aimed to identify glycine analogs conducive to the formation of cell-absorbable nanocomplexes, enhancing Collagen synthesis and subsequent osteogenesis in combination with BMP2 for improved bone regeneration.

Methods: Glycine and its derivatives were assessed for their effects on osteogenic differentiation in MC3T3-E1 cells and human bone marrow mesenchymal stem cells (BMSCs) under osteogenic conditions or with BMP2. Osteogenic differentiation was assessed through Alkaline Phosphatase staining and real-time quantitative polymerase chain reaction (RT-qPCR). Nanocomplex formation was examined via scanning electron microscopy, circular dichroism, and ultraviolet-visible spectroscopy. In vivo osteogenic effects were validated using a mouse calvarial defect model, and bone regeneration was evaluated through micro-computed tomography and histomorphometric analysis.

Results: Glycine, glycine methyl ester, and glycinamide significantly enhanced Collagen synthesis and ALP activity in conjunction with an osteogenic medium (OSM). GA emerged as the most effective inducer of osteoblast differentiation marker genes. Combining GA with BMP2 synergistically stimulated ALP activity and the expression of osteoblast markers in both cell lines. GA readily formed nanocomplexes, facilitating cellular uptake through strong electrostatic interactions. In an in vivo calvarial defect mouse model, the GA and BMP2 combination demonstrated enhanced bone volume, bone volume/tissue volume ratio, trabecular numbers, and mature bone formation compared to Other combinations.

Conclusion: GA and BMP2 synergistically promoted in vitro osteoblast differentiation and in vivo bone regeneration through nanocomplex formation. This combination holds therapeutic promise for individuals with bone defects, showcasing its potential for clinical intervention.

Keywords

Bone morphogenetic protein 2; Bone regeneration; Glycinamide HCl.

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