Yakovenchuk N. N.

EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN ARTICULAR CARTILAGE AND SUBCHONDRAL BONE IN OSTEOARTHRITIS (EXPERIMENTAL STUDY)


About the author:

Yakovenchuk N. N.

Heading:

MORPHOLOGY

Type of article:

Scentific article

Annotation:

The pathogenesis of disorders in articular cartilage is considered in unity with the state of the subchondral bone. In the field of view of the researchers is vascular endothelial growth factor (VEGF), which is an important mediator of endochondral ossification; development and growth of the skeleton. The aim of the study was to study the expression of VEGF by articular cartilage chondrocytes and osteocytes of the rat knee joint subchondral bone under conditions of osteoarthrosis modeling by ovariectomy. Object and methods. The experiment was conducted on 12 laboratory rats. The method of ovariectomy is used, since it is known that along with the development of osteoporosis in animals’ arthrosis develops. The histological study of knee joint condition in animals after ovariectomy was performed for the determination of changes in the joint with subsequent evaluation of VEGF by immunohistochemical study. The knee joints of healthy rats were used as a control for an immunohistochemical reaction. Results. By histological examination it is established that after 3 months in rats after ovariectomy in the articular cartilage of the knee joint (of the femur and tibia), histopathological changes occurred. First of all, we observed a weakly pronounced fibrillation of articular cartilage matrix, which most manifested itself in the medial part of the femur; reduced chondrocyte density and disturbance in their distribution in articular cartilage zones. It has been established that at early stages of development of arthritic changes in articular cartilage, chondrocytes have positive VEGF immunoreactivity in all areas of articular cartilage, in contrast to control animals in which VEGF is detected only in the area of hypertrophied cartilage. In the study of the subchondral bone, it was found that only single osteocytes had positive VEGF immunoreactivity. Basically, an increased density of cells that express VEGF is found in the bone marrow cavities, where multipotent progenitor cells of chondrocytes, osteoblasts, endothelial cells, etc. are located. Since VEGF reflects vascular invasion, it shows an imbalance of bone-cartilage interaction at early stages of development osteoarthritis. Conclusion. On the basis of immunohistochemical research it was determined that in conditions of osteoarthritis, expression of VEGF is observed in cells of all zones of articular cartilage. The level of VEGF expression is low in subchondral bone. Understanding the importance of the relationship between articular cartilage and subchondral bone through the system of VEGF in conditions of arthrosis will enhance the knowledge about the mechanisms of development of disorders and will contribute to the improvement of pathogenetic approaches in the conservative treatment strategy.

Tags:

vascular endothelial growth factor, osteoarthritis modeling, knee joint, articular cartilage, subchondral bone

Bibliography:

  1. Korzh NA, Dedukh NV, Yakovenchuk NN. Osteoporoz i osteoartroz: patogeneticheski vzaimosvyazannyie zabolevaniya? (obzor literatury). Ortopediya, travmatologiya i protezirovanie. 2013;4:102-10. [in Russian].
  2. Dai J, Rabie AB. VEGF: an essential mediator of both angiogenesis and endochondral ossification. J. Dent Res. 2007;86(10):937-50. DOI: 10.1177/154405910708601006
  3.  Nagao M, Hamilton JL, Kc R, Berendsen AD, Duan X, Cheong CW, et al. Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis. Scientific Reports. 2017;7. DOI: https://doi.org/10.1038/s41598-017-13417-w
  4.  Zelzer E, Olsen BR. Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair. Curr Top Dev Biol. 2005;65:169-87. DOI: 10.1016/S0070-2153(04)65006-X
  5.  Pfander D, Körtje D, Zimmermann R, Weseloh G, Kirsch T, Gesslein M, et al. Vascular endothelial growth factor in articular cartilage of healthy and osteoarthritic human knee joints. Ann Rheum Dis. 2001;60:1070-3.
  6. Pufe T, Petersen W, Tillmann B, Mentlein R. The splice variants VEGF121 and VEGF189 of the angiogenic peptide vascular endothelial growth factor are expressed in osteoarthritic cartilage. Arthritis Rheum. 2001;44:1082-8. Available from: https://doi.org/10.1002/1529- 0131(200105)44:53.0.CO;2-X
  7.  Povoroznyuk VV, Grigoreva NV. Osteoartroz u zhenshin v postmenopauze: faktory riska i svyaz s kostnoj tkanyu. Endokrinologiya. 2012;6(8):64- 71. [in Russian].
  8. Yakovenchuk NM, Dedukh NV. Morfologiya suglobovogo hryasha ta subhondralnoyi kistki pislya modelyuvannya osteoporozu. Visnik problem biologiyi i medicini. 2017;4,3(141):324-7. DOI: 10.29254/2077–4214–2017–4–3–141–324-327 [in Ukrainian].
  9.  Evropeyska konventsіya pro zahist hrebetnih tvarin, scho vikoristovuyutsya dlya doslidnih ta inshih naukovih tsiley. Strasburg, 18 bereznya 1986 roku: ofItsiyniy pereklad [Internet]. Verhovna Rada Ukrayni. Ofіts. veb-sayt. (Mіzhnarodniy dokument Radi Evropi). Dostupno: http: zakon.rada.gov.ua/cgi-bin/laws/main.cgi?nreg=994_137 [in Ukrainian].
  10. Zakon Ukrayini № 3447-IV vіd 21.02.2006 «Pro zahist tvarin vid zhorstokogo povodzhennya» (Stattya 26). [in Ukrainian].
  11. Sarkisov DS, Perov YuL. Mikroskopicheskaya tehnika. M.: Meditsina; 1996. 544 s. [in Russian].
  12. Mankin H, Dorfman H, Lippiellon L, Zarins A. Biochemical and metabolicabnormalitics in articular cartilage from osteoarthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J. Bone Joint Surg. Am. 1971;53:523-37.
  13. Hamilton JL, Nagao M, Levine BR, Chen D, Olsen BR, Im H-J. Targeting VEGF and its receptors for the treatment of osteoarthritis and associated pain. J. Bone Miner. Res. 2016;31:911-24. Available from: https://doi.org/10.1002/jbmr.2828
  14.  Yamairi F, Utsumi H, Ono Y, Komorita N, Tanaka M, Fukunari A. Expression of vascular endothelial growth factor (VEGF) associated with histopathological changes in rodent models of osteoarthritis. J.Toxicol.Pathol. 2011;24:137-42. DOI: 10.1293/tox.24.137
  15. Enomoto H, Inoki I, Komiya K, Shiomi T, Ikeda E, Obata K, et al. Vascular endothelial growth factor isoforms and their receptors are expressed in human osteoarthritic cartilage. Am J Pathol. 2003;162:171-81.
  16. Yuan Q, Sun L, Li JJ, An CH. Elevated VEGF levels contribute to the pathogenesis of osteoarthritis. BMC Musculoskelet Disord. 2014;15:437. Available from: https://doi.org/10.1186/1471-2474-15-437
  17. Hu K, Olsen BR. Osteoblast-derived VEGF regulates osteoblast differentiation and bone formation during bone repair. J Clin. Invest. 2016;126:509-26. Available from: https://doi.org/10.1172/JCI82585
  18. Liu Y, Berendsen AD, Jia S, Lotinun S, Baron R, Olsen BR, et al. Intracellular VEGF regulates the balance between osteoblast and adipocyte diferentiation. J Clin Invest. 2012;122:3101-13. Available from: https://doi.org/10.1172/JCI61209
  19.  Mayr-Wohlfart U, Waltenberger J, Hausser H, Kessler S, Günther KP, Dehio C, et al. Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts. Bone. 2002;30(3):472-7.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 1 Part 2 (149), 2019 year, 313-316 pages, index UDK 616.72-007.248

DOI: