Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo
Abstract
:1. Introduction
2. Results
2.1. Crystallography of Calcium Chelidonate ([Ca(ChA)(H2O)3]n)
2.2. In Vitro and In Vivo Study of the Osteoinductive Activity of Calcium Chelidonate
3. Discussion
4. Materials and Methods
4.1. General Experimental Procedures
4.2. Semi-Synthesis of Calcium Chelidonate
4.3. Characterization of Calcium Chelidonate ([Ca(ChA)(H2O)3]n)
4.4. Cell Isolation
4.5. In Vitro Cell Culturing and Alizarin Red Staining
4.6. Ectopic Osteogenesis Test to Study In Situ Osteogenic Activity of Calcium Chelidonate
4.7. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Bonds, (Å) | |||
---|---|---|---|
Ca1–O1 | 2.630(2) | Ca1–O10 | 2.459(2) |
Ca1–O2 | 2.480(2) | Ca1–O11 | 2.419(3) |
Ca1–O3 | 2.397(3) | Ca1–O2_a | 2.483(3) |
Ca1–O4 | 2.330(3) | Ca1–O10_a | 2.555(2) |
Angles, (°) | |||
O1–Ca1–O2 | 127.95(8) | O2–Ca1–O2_a | 115.13(8) |
O1–Ca1–O3 | 79.59(9) | O2–Ca1–O10_a | 76.73(7) |
O1–Ca1–O4 | 131.19(8) | O3–Ca1–O4 | 77.93(10) |
O1–Ca1–O10 | 61.84(7) | O3–Ca1–O10 | 77.64(8) |
O1–Ca1–O11 | 61.18(7) | O3–Ca1–O11 | 3.38(9) |
O1–Ca1–O2_a | 71.63(7) | O3–Ca1–O2_a | 150.01(9) |
O1–Ca1–O10_a | 137.97(6) | O3–Ca1–O10_a | 142.42(8) |
O2–Ca1–O3 | 76.38(9) | O4–Ca1–O10 | 148.79(9) |
O2–Ca1–O4 | 87.34(9) | O4–Ca1–O11 | 77.56(9) |
O2–Ca1–O10 | 68.22(7) | O4–Ca1–O2_a | 128.01(9) |
O2–Ca1–O11 | 163.33(8) | O4–Ca1–O10_a | 75.06(8) |
Hydrogen Bond | O/C–H, (Å) | H…O, (Å) | O/C…A, (Å) | O/C–H…A, (°) |
---|---|---|---|---|
intra–complex | ||||
O2–H2A…O12 | 0.83(3) | 1.81(4) | 2.602(3) | 160(4) |
O3–H3A…O11 | 0.84(3) | 2.20(3) | 3.024(4) | 166(4) |
inter–complex | ||||
O2–H2B…O9 | 0.84(4) | 1.98(4) | 2.789(3) | 163(3) |
O3–H3B…O4 | 0.84(3) | 2.35(4) | 3.043(4) | 139(5) |
O3–H3B…O11 | 0.84(3) | 2.38(4) | 3.094(4) | 142(5) |
O4–H4A…O9 | 0.84(3) | 1.89(3) | 2.721(4) | 170(3) |
O4–H4B…O13 | 0.85(4) | 1.87(4) | 2.686(4) | 162(4) |
C5–H5…O12 | 0.93 | 2.42 | 3.327(4) | 166 |
The Groups Studied, n = 5 | The Incidence of Tissue Lamella Growth on CaP Surface | The Incidence of Ectopic Bone Formation in Lamella | Bone Marrow Column Seeded In Vitro on CaP Coating (Initial Levels before Implantation) | Tissue Lamella Properties In Situ (after Implantation) | ||||
---|---|---|---|---|---|---|---|---|
% | % | Area, mm2 | Area of Tissue Lamellae, mm2 | Number of Calculated Cross Sections Per Lamella | Part of Cross Sections with bone, % | Area of Newborn Bone Per Cross Section, mm2 | Histological Composition | |
CaP-coated samples under the skin + water solvent per os (control) | 80 (4/5) | 75 (3/4) | 7.65 (6.63–8.17) | 23.65 (18.40–31.90) | 141 (36–167) | 78 (31–100) | 0.21 (0.13–0.24) | Bone with marrow (Figure 4a–c) in 3 cases; connective and adipose tissues (not shown) in 1 case |
CaP-coated samples under the skin + CaChA per os, 10 mg/kg | 100 | 100 | 6.27 (5.94–7.36) | 57.40 * (42.00–60.40) | 89 (81–132) | 100 (96–100) | 0.20 (0.07–0.23) | Bone tissue with bone marrow (Figure 4d–h) in 5 cases |
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Avdeeva, E.; Porokhova, E.; Khlusov, I.; Rybalova, T.; Shults, E.; Litvinova, L.; Shupletsova, V.; Khaziakhmatova, O.; Sukhodolo, I.; Belousov, M. Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo. Pharmaceuticals 2021, 14, 579. https://doi.org/10.3390/ph14060579
Avdeeva E, Porokhova E, Khlusov I, Rybalova T, Shults E, Litvinova L, Shupletsova V, Khaziakhmatova O, Sukhodolo I, Belousov M. Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo. Pharmaceuticals. 2021; 14(6):579. https://doi.org/10.3390/ph14060579
Chicago/Turabian StyleAvdeeva, Elena, Ekaterina Porokhova, Igor Khlusov, Tatyana Rybalova, Elvira Shults, Larisa Litvinova, Valeria Shupletsova, Olga Khaziakhmatova, Irina Sukhodolo, and Mikhail Belousov. 2021. "Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo" Pharmaceuticals 14, no. 6: 579. https://doi.org/10.3390/ph14060579