Bone Morphogenetic Protein (BMP-2/BMP-7) Heterodimer and BMPR1A, BMPR2 Polymorphism in Simple Fractures among Sudanese Patients

Authors

  • Amin Ali Department of Biochemistry, University of Khartoum, Khartoum, Sudan
  • Maowia Mukhtar Department of Molecular Biology, Institute of Endemic Disease, University of Khartoum, Khartoum, Sudan
  • Samir Shaheen Department of Orthopedic Surgery and Traumatology, University of Khartoum, Khartoum, Sudan
  • Abdelrahim Mohamed Osman Department of Biochemistry, University of Khartoum, Khartoum, Sudan

DOI:

https://doi.org/10.3889/oamjms.2023.11555

Keywords:

BMPR1 polymorphism, BMPR2 polymorphism, Fracture healing biology, BMP-2/-7 heterodimer

Abstract

Background: bone morphogenetic proteins are responsible for activating mesenchymal stem cells into osteocytes. This effect is signaled by serine-threonine kinase receptors called bone morphogenetic protein receptors. BMPR1A and BMPR2 polymorphisms were not reported to be associated with bone healing process. The objective of this study was to investigate BMP-2/-7 heterodimer and BMPR1A/ BMPR2 polymorphism with fracture healing progress.

Subjects and Methods: This is a case-control study conducted in selected hospitals in Khartoum, Sudan. Blood samples were taken from patients and healthy controls. Followed by clinical examination until the point of functional recovery. Quantitative ELISA and protein-pull down assay were done to BMP-2 and BMP-7. Genomic DNA extraction and PCR/RFP and sequencing were done to BMPR1A and BMPR2 target sequences.

Results: Matched case and control groups in age and gender. Functional outcome regained after 4.1 months ± 2.6. BMP2/7 complex levels were 288.75pg/ml ± 266.8 and 532.23 pg/ml ±582.5 in case and control, respectively (p= 0.021). BMPR2 exhibited single nucleotide polymorphism among all participants; while there was 25% and 22% had variant [A] BMPR1A, 75% and 78% [T] variant BMPR1A in case and control, respectively.

Conclusion: Significant change in plasma BMP-2/-7 heterodimer concentration was observed after trauma but no significant correlation between BMPR1A and BMPR2 polymorphism with fracture healing.

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References

Sánchez-Duffhues G, Hiepen C, Knaus P, Ten Dijke P. Bone morphogenetic protein signaling in bone homeostasis. Bone. 2015;80:43-59. https://doi.org/10.1016/j.bone.2015.05.025 PMid:26051467 DOI: https://doi.org/10.1016/j.bone.2015.05.025

Dumic-Cule I, Peric M, Kucko L, Grgurevic L, Pecina M, Vukicevic S. Bone morphogenetic proteins in fracture repair. Int Orthop. 2018;42(11):2619-26. https://doi.org/10.1007/s00264-018-4153-y PMid:30219967 DOI: https://doi.org/10.1007/s00264-018-4153-y

Lin S, Svoboda KK, Feng JQ, Jiang X. The biological function of Type I receptors of bone morphogenetic protein in bone. Bone Res. 2016;4:16005. https://doi.org/10.1038/boneres.2016.5 PMid:27088043 DOI: https://doi.org/10.1038/boneres.2016.5

Yu S, Guo J, Sun Z, Lin C, Tao H, Zhang Q, et al. BMP2- dependent gene regulatory network analysis reveals Klf4 as a novel transcription factor of osteoblast differentiation. Cell Death Dis. 2021;12(2):197. https://doi.org/10.1038/s41419-021-03480-7 PMid:33608506 DOI: https://doi.org/10.1038/s41419-021-03480-7

Scarfì S. Use of bone morphogenetic proteins in mesenchymal stem cell stimulation of cartilage and bone repair. World J Stem Cells. 2016;8(1):1-12. https://doi.org/10.4252/wjsc.v8.i1.1 PMid:26839636 DOI: https://doi.org/10.4252/wjsc.v8.i1.1

Kaito T, Morimoto T, Mori Y, Kanayama S, Makino T, Takenaka S, et al. BMP-2/7 heterodimer strongly induces bone regeneration in the absence of increased soft tissue inflammation. Spine J. 2018;18(1):139-46. https://doi.org/10.1016/j.spinee.2017.07.171 PMid:28735764 DOI: https://doi.org/10.1016/j.spinee.2017.07.171

Katagiri T, Watabe T. Bone morphogenetic proteins. Cold Spring Harb Perspect Biol. 2016;8(6):a021899. https://doi.org/10.1101/cshperspect.a021899 PMid:27252362 DOI: https://doi.org/10.1101/cshperspect.a021899

Gomez-Puerto MC, Iyengar PV, de Vinuesa AG, Ten Dijke P, Sanchez-Duffhues G. Bone morphogenetic protein receptor signal transduction in human disease. J Pathol. 2019;247(1): 9-20. https://doi.org/10.1002/path.5170 PMid:30246251 DOI: https://doi.org/10.1002/path.5170

Barnes JW, Kucera ET, Tian L, Mellor NE, Dvorina N, Baldwin WW 3rd, et al. Bone morphogenic protein Type 2 receptor mutation-independent mechanisms of disrupted bone morphogenetic protein signaling in idiopathic pulmonary arterial hypertension. Am J Respir Cell Mol Biol. 2016;55(4):564-75. https://doi.org/10.1165/rcmb.2015-0402OC PMid:27187737 DOI: https://doi.org/10.1165/rcmb.2015-0402OC

Rahman MS, Akhtar N, Jamil HM, Banik RS, Asaduzzaman SM. TGF-β/BMP signaling and other molecular events: Regulation of osteoblastogenesis and bone formation. Bone Res. 2015;3:15005. https://doi.org/10.1038/boneres.2015.5 PMid:26273537 DOI: https://doi.org/10.1038/boneres.2015.5

Islam MJ, Parves MR, Mahmud S, Tithi FA, Reza MA. Assessment of structurally and functionally high-risk nsSNPs impacts on human bone morphogenetic protein receptor Type IA (BMPR1A) by computational approach. Comput Biol Chem. 2019;80:31-45. https://doi.org/10.1016/j.compbiolchem.2019.03.004 PMid:30884445 DOI: https://doi.org/10.1016/j.compbiolchem.2019.03.004

Wang T, Zhang X, Bikle DD. Osteogenic differentiation of periosteal cells during fracture healing. J Cell Physiol. 2017;232(5):913-21. https://doi.org/10.1002/jcp.25641 PMid:27731505 DOI: https://doi.org/10.1002/jcp.25641

Yang J, Shi P, Tu M, Wang Y, Liu M, Fan F, et al. Bone morphogenetic proteins: Relationship between molecular structure and their osteogenic activity. Food Sci Hum Wellness. 2014;3(3-4):127-35. DOI: https://doi.org/10.1016/j.fshw.2014.12.002

Rigueur D, Brugger S, Anbarchian T, Kim JK, Lee Y, Lyons KM. The Type I BMP receptor ACVR1/ALK2 is required for chondrogenesis during development. J Bone Miner Res. 2015;30(4):733-41. https://doi.org/10.1002/jbmr.2385 PMid:25413979 DOI: https://doi.org/10.1002/jbmr.2385

Pan H, Zhang H, Abraham P, Komatsu Y, Lyons K, Kaartinen V, et al. BmpR1A is a major Type 1 BMP receptor for BMP-Smad signaling during skull development. Dev Biol. 2017;429(1):260-70. https://doi.org/10.1016/j.ydbio.2017.06.020 PMid:28641928 DOI: https://doi.org/10.1016/j.ydbio.2017.06.020

Louche A, Salcedo SP, Bigot S. Protein-protein interactions: Pull-down assays. Methods Mol Biol. 2017;1615:247-55. https://doi.org/10.1007/978-1-4939-7033-9_20 PMid:28667618 DOI: https://doi.org/10.1007/978-1-4939-7033-9_20

Kohl TO, Ascoli CA. Immunometric Double-Antibody Sandwich Enzyme-Linked Immunosorbent Assay. Cold Spring Harb Protoc [Internet]. 2017;2017(6):pdb.prot093724. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28572188 DOI: https://doi.org/10.1101/pdb.prot093724

Ye YW, Ling N, Han YJ, Wu QP. Detection and prevalence of pathogenic Yersinia enterocolitica in refrigerated and frozen dairy products by duplex PCR and dot hybridization targeting the virF and ail genes. J Dairy Sci. 2014;97(11):6785-91. https://doi.org/10.3168/jds.2014-8382 PMid:25218752 DOI: https://doi.org/10.3168/jds.2014-8382

Kaczmarczyk M, Goracy I, Loniewska B, Kuprjanowicz A, Binczak-Kuleta A, Clark JS, et al. Association of BMPR1A polymorphism, but not BMP4, with kidney size in full-term newborns. Pediatr Nephrol. 2013;28(3):433-8. https://doi.org/10.1007/s00467-012-2277-7 PMid:22886282 DOI: https://doi.org/10.1007/s00467-012-2277-7

Van der Bruggen CE, Happé CM, Dorfmüller P, Trip P, Spruijt OA, Rol N, et al. Bone morphogenetic protein receptor Type 2 mutation in pulmonary arterial hypertension: A view on the right ventricle. Circulation. 2016;133(18):1747-60. https://doi.org/10.1161/circulationaha.115.020696 PMid:26984938 DOI: https://doi.org/10.1161/CIRCULATIONAHA.115.020696

Huo T, Guo Y, Shenkman E, Muller K. Assessing the reliability of the short form 12 (SF-12) health survey in adults with mental health conditions: A report from the wellness incentive and navigation (WIN) study. Health Qual Life Outcomes. 2018;16(1):34. https://doi.org/10.1186/s12955-018-0858-2 PMid:29439718 DOI: https://doi.org/10.1186/s12955-018-0858-2

Li Z, Lang G, Karfeld-Sulzer LS, Mader KT, Richards RG, Weber FE, et al. Heterodimeric BMP-2/7 for nucleus pulposus regeneration-in vitro and ex vivo studies. J Orthop Res. 2017;35(1):51-60. https://doi.org/10.1002/jor.23351 PMid:27340938 DOI: https://doi.org/10.1002/jor.23351

Agnew C, Ayaz P, Kashima R, Loving HS, Ghatpande P, Kung JE, et al. Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization. Nat Commun. 2021;12(1):4950. https://doi.org/10.1038/s41467-021-25248-5 PMid:34400635 DOI: https://doi.org/10.1038/s41467-021-25248-5

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Published

2023-04-02

How to Cite

1.
Ali A, Mukhtar M, Shaheen S, Osman AM. Bone Morphogenetic Protein (BMP-2/BMP-7) Heterodimer and BMPR1A, BMPR2 Polymorphism in Simple Fractures among Sudanese Patients. Open Access Maced J Med Sci [Internet]. 2023 Apr. 2 [cited 2024 May 2];11(A):195-9. Available from: https://oamjms.eu/index.php/mjms/article/view/11555