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Deneysel Osteoporoz Oluşturulan Ratlarda Beyin Natriüretik Peptid Düzeyinin Biyokimyasal Belirteçler, Kemik Mineral Yoğunluğu ve Progenitör Faktörlerle İlişkisi

Year 2022, Volume: 7 Issue: 1, 5 - 12, 01.04.2022

Abstract

DENEYSEL OSTEOPOROZ OLUŞTURULAN RATLARDA BEYİN NATRİÜRETİK PEPTİD DÜZEYİNİN BİYOKİMYASAL BELİRLEYİCİLER, KEMİK MİNERAL YOĞUNLUĞU VE PROGENİTÖR FAKTÖRLERLE İLİŞKİSİNİN İNCELENMESİ
ÖZET
Amaç: Deneysel osteoporoz oluşturulan ratlarda plazma beyin natriüretik peptid (BNP) düzeyinin kemik mineral yoğunluğu (KMY), kemik döngüsünün biyokimyasal belirleyicileri ve progenitör faktörler ile olan ilişkisinin araştırılması amaçlanmıştır.
Materyal ve Metod: Bu çalışmada ağırlığı 240-280 gr arasında değişen 36 adet Wistar-Albino tipi rat (18 erkek ve 18 dişi) deneysel osteoporoz ve kontrol grupları oluşturmak üzere eşit olarak dört gruba ayrıldı. Osteoporoz için dişi ratlara ovariektomi [ovariektomize grup (OVX) (n=9)] ve erkek ratlara orşiektomi [orşiektomize grup (ORX) (n=9)] cerrahi işlemi uygulandı. Cerrahi işlemden dört ay sonra tüm ratların kemik yapım belirleyicilerinden plazma kalsiyum (Ca), fosfor (P), alkalen fosfataz (ALP) ve osteokalsin (OK) düzeyleri ve kemik yıkım belirleyicilerinden plazma ve idrar C-telopeptid (CTX) düzeyleri ve kemik üzerine progenitör etkili sitokinlerden insülin benzeri büyüme faktörü-I (IGF-I) ve transforming growth faktör-β1 (TGF-β1) düzeyleri ve BNP düzeylerini değerlendirmek için kan ve idrar örnekleri alındı. Ayrıca lumbal ve proksimal femur KMY’leri Dual enerji x-ray absorbsiyometri kullanılarak değerlendirildi.
Bulgular: Osteoporoz oluşturulan OVX ve ORX gruplarında kontrol gruplarına göre lumbal ve femur bölgelerinde KMY değerleri istatistiksel olarak anlamlı düşük bulundu (p<0.05). Ovariektomize ile dişi kontrol grubu (n=9) arasında ve orşiektomize ile erkek kontrol grubu (n=9) arasında plazma ALP, OK, CTX plazma ve CTX idrar değerleri osteoporoz oluşturulan gruplarda kontrol gruplarından istatistiksel olarak anlamlı düzeyde yüksek bulundu (p<0.05). Ca ve P değerlerinde ise bir farklılık gözlenmedi. BNP ve TGF-β1 değerleri osteoporoz oluşturulan gruplarda kontrol gruplarına kıyasla istatistiksel olarak anlamlı bir şekilde daha düşük bulundu (p<0.05). IGF-I düzeylerinde gruplar arasında anlamlı farklılık yoktu. Osteoporotik gruplarda BNP değerleri ile KMY ve TGF-β1 değerleri arasında pozitif korelasyon saptandı (sırasıyla, r=0,636; p=0,01 ve r= 0,653; p=0,036). BNP ile IGF-I ve biyokimyasal belirleyiciler arasında anlamlı korelasyon yoktu (p>0.05).

Sonuç: Deneysel osteoporoz oluşturulan ratlarda plazma ve idrar BNP düzeyleri daha düşük bulundu. Ayrıca ratların KMY’leri ile plazma ve idrar BNP düzeyleri arasında pozitif korelasyon saptandı. Bu bulgular osteoporoz etyopatogenezinde BNP’nin rolünün olabileceğini düşündürmektedir.

References

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  • 2. Kanis JA, Gluer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int 2000;11:192-202.
  • 3. Nancy L, Dequeker J, Gregory R. Bone structure and function. In: Marc C Hochberg, Alan J Silman, Josef S Smolen et al. Rheumatology. WB Saunders Company, Philadelphia 2003:2029-2041.
  • 4. Guyton AC. Textbook of Medikal Physiology (11 th ed). Williams & Wilkins, Baltimore 2006; pp 979-995.
  • 5. Kutlu M. Kemik doku ve fizyolojisi; In: Yılmaz C (ed), Tüm Yönleriyle Osteoporoz. Bilimsel Tıp Yayınevi, Ankara 1997, 5-29.
  • 6. Delmas PD. Markers of bone formation and resorption. In: Favus (ed), Primer On the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Lippincott Raven, New York 1993; pp 16-31.
  • 7. Hagiwara H, Sakaguchi H, Itakura M, et al. Autocrine regulation of rat chondrocyte proliferation by natriuretic peptide C and its receptor, natriuretic peptide receptor. J Biol Chem 1994 Apr 8;269(14):10729-33.
  • 8. Suda M, Ogawa Y, Tanaka K, et al. Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide. Proc Natl Acad 1998;95:2337-42.
  • 9. Frost HM, Jee WS. On the rat model human osteopenias and osteoporosis. Bone and Mineral 1992;18:227-236.
  • 10. Norimatsu H, Mori S, Kawanishi J, et al. immobilization as the pathogenesis of osteoporosis; Experimental and klinical studies. Osteoporosis Int 1997;7:57-62.
  • 11. Kimmel DB. Animal models for in vivo experimentation in osteoporosis research; Markus R, Feldman D, Kelsey J (ed), Osteoporosis. Academic Press, San Diego 1996, pp. 671-690.
  • 12. Audran M, Chappard D, Legrand E et all. Bone microarchitecture and bone fragility in men: DEXA and histomorphometry in humans and in the orchidectomized rat model. Calcif Tissue Int. 2001 Oct;69(4):214-7.
  • 13. Wang X, Wang M, Cui X, et al. Antiosteoporosis effect of geraniin on ovariectomy-induced osteoporosis in experimental rats. J Biochem Mol Toxicol. 2021;35(6):1-8.
  • 14. Melhus G, Solberg LB, Dimmen S et all. Experimental osteoporosis induced by ovariectomy and vitamin D deficiency does not markedly affect fracture healing in rats. Acta Orthop. 2007 Jun;78(3):393-403.
  • 15. Jain S, Camacho P. Use of bone turnover markers in the management of osteoporosis. Curr Opin Endocrinol Diabetes Obes. 2018;25(6):366-372.
  • 16. Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 1996;11(3):337-49.
  • 17. Hlaing TT, Compston JE. Biochemical markers of bone turnover - uses and limitations. Ann Clin Biochem. 2014;51(Pt 2):189-202.
  • 18. Sepici V. Osteoporoz tanı ve takibinde laboratuar yöntemleri. In: Gökçe YK (ed). Osteoporoz. Güneş yayınevi, İstanbul 1998, pp. 104-118.
  • 19. Ohta H, Ikeda T, Masuzawa T, et al. Differences in axial bone mineral density, serum levels of sex steroids and bone metabolism between postmenopausal age and body size atched premenopausal subjects. Bone 1993;14(2):111-6.
  • 20. Minura H, Yamamoto I, Yuu I, Ohta T. Estimation of bone mineral density and bone loss by means of bone metabolic markers in postmenopausal women. Endoc J 1995;42(6):797-802.
  • 21. Garnero P, Delmas P. Biochemical markers of bone turneover. Applications for steoporosis. Endocrinol Metab Clin North Am 1998;27(2):303-23.
  • 22. Worsfold M, Powell DE, Jones TJ, Davie MW. Assessment of urinary bone markers for monitoring treatment of osteoporosis. Clin Chem 2004;7:324-8.
  • 23. Chaki O, Yoshikata I, Kikuchi R, Nakayama M, Uchiyama Y, Hirahara F, et al. The predictive value of biochemical markers of bone turnover for bone mineral density in ostmenopausal osteoporosis. J Bone Miner Res 2000;15(8):1537-44.
  • 24. Matsukawa N.Grzesik W.j.Tagahashi N, et al. The natriüretic peptide clearence reseptor lokally modulates the physiological effects of the natriuretic peptide systems. Proc Natl Acad 1999;96:7403-7408.
  • 25. Kajita M, Ezura Y, Iwasaki H, et al. Association of the -381T/C promoter variation of the brain natriuretic peptide gene with low bone-mineral density and rapid postmenopausal bone loss. J Hum Genet 2003;48(2):77-81.
  • 26. Nasu M, Sugimoto T, Chihara M, Hiraumi M, Kurimoto F, Chihara K. Effect of natural menopause on serum levels of IGF-I and IGFbinding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women. Eur J Endocrinol 1997;136(6):608- 616.
  • 27. López-Quiles J, Forteza-López A, Montiel M, Clemente C, Fernández-Tresguerres JA, Fernández-Tresguerres I. Effects of locally applied Insulin-like Growth Factor-I on osseointegration. Med Oral Patol Oral Cir Bucal. 2019;24(5):652-658.
  • 28. Ebeling PR, Jones JD, O’ fallon WM, et al. Short-term effects of recombinant human insulın-like growth factor I on bone turnover in normal women. J Clin Endocrinol Metab 1993;77:1384-1387.
  • 29. Reddi A. BMPs: from bone morphogenetic proteins to body morphogenetic proteins. Cytokine Growth Factor Rev 2005;16:249-250.
  • 30. Nasu M, Sugimoto T, Chihara M, Hiraumi M, Kurimoto F, Chihara K. Effect of natural menopause on serum levels of IGF-I and IGFbinding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women. Eur J Endocrinol 1997;136(6):608- 616.
  • 31. Nicolas V, Prewett A, Bettica P, et al. Age-related decreases in insulin-like growth factor-I and transforming growth factor-beta in femoral cortical bone from both men and women: implications for bone loss with aging. Clin Endocrinol Metab 1994 May;78(5):1009-10.
Year 2022, Volume: 7 Issue: 1, 5 - 12, 01.04.2022

Abstract

References

  • KAYNAKLAR 1. Eryavuz M. Osteoporozun tanımı ve sınıflandırması; In: Kutsal Y.G. (Ed) Osteoporoz. Güneş yayınevi, İstanbul 2005; 1-7.
  • 2. Kanis JA, Gluer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int 2000;11:192-202.
  • 3. Nancy L, Dequeker J, Gregory R. Bone structure and function. In: Marc C Hochberg, Alan J Silman, Josef S Smolen et al. Rheumatology. WB Saunders Company, Philadelphia 2003:2029-2041.
  • 4. Guyton AC. Textbook of Medikal Physiology (11 th ed). Williams & Wilkins, Baltimore 2006; pp 979-995.
  • 5. Kutlu M. Kemik doku ve fizyolojisi; In: Yılmaz C (ed), Tüm Yönleriyle Osteoporoz. Bilimsel Tıp Yayınevi, Ankara 1997, 5-29.
  • 6. Delmas PD. Markers of bone formation and resorption. In: Favus (ed), Primer On the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Lippincott Raven, New York 1993; pp 16-31.
  • 7. Hagiwara H, Sakaguchi H, Itakura M, et al. Autocrine regulation of rat chondrocyte proliferation by natriuretic peptide C and its receptor, natriuretic peptide receptor. J Biol Chem 1994 Apr 8;269(14):10729-33.
  • 8. Suda M, Ogawa Y, Tanaka K, et al. Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide. Proc Natl Acad 1998;95:2337-42.
  • 9. Frost HM, Jee WS. On the rat model human osteopenias and osteoporosis. Bone and Mineral 1992;18:227-236.
  • 10. Norimatsu H, Mori S, Kawanishi J, et al. immobilization as the pathogenesis of osteoporosis; Experimental and klinical studies. Osteoporosis Int 1997;7:57-62.
  • 11. Kimmel DB. Animal models for in vivo experimentation in osteoporosis research; Markus R, Feldman D, Kelsey J (ed), Osteoporosis. Academic Press, San Diego 1996, pp. 671-690.
  • 12. Audran M, Chappard D, Legrand E et all. Bone microarchitecture and bone fragility in men: DEXA and histomorphometry in humans and in the orchidectomized rat model. Calcif Tissue Int. 2001 Oct;69(4):214-7.
  • 13. Wang X, Wang M, Cui X, et al. Antiosteoporosis effect of geraniin on ovariectomy-induced osteoporosis in experimental rats. J Biochem Mol Toxicol. 2021;35(6):1-8.
  • 14. Melhus G, Solberg LB, Dimmen S et all. Experimental osteoporosis induced by ovariectomy and vitamin D deficiency does not markedly affect fracture healing in rats. Acta Orthop. 2007 Jun;78(3):393-403.
  • 15. Jain S, Camacho P. Use of bone turnover markers in the management of osteoporosis. Curr Opin Endocrinol Diabetes Obes. 2018;25(6):366-372.
  • 16. Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 1996;11(3):337-49.
  • 17. Hlaing TT, Compston JE. Biochemical markers of bone turnover - uses and limitations. Ann Clin Biochem. 2014;51(Pt 2):189-202.
  • 18. Sepici V. Osteoporoz tanı ve takibinde laboratuar yöntemleri. In: Gökçe YK (ed). Osteoporoz. Güneş yayınevi, İstanbul 1998, pp. 104-118.
  • 19. Ohta H, Ikeda T, Masuzawa T, et al. Differences in axial bone mineral density, serum levels of sex steroids and bone metabolism between postmenopausal age and body size atched premenopausal subjects. Bone 1993;14(2):111-6.
  • 20. Minura H, Yamamoto I, Yuu I, Ohta T. Estimation of bone mineral density and bone loss by means of bone metabolic markers in postmenopausal women. Endoc J 1995;42(6):797-802.
  • 21. Garnero P, Delmas P. Biochemical markers of bone turneover. Applications for steoporosis. Endocrinol Metab Clin North Am 1998;27(2):303-23.
  • 22. Worsfold M, Powell DE, Jones TJ, Davie MW. Assessment of urinary bone markers for monitoring treatment of osteoporosis. Clin Chem 2004;7:324-8.
  • 23. Chaki O, Yoshikata I, Kikuchi R, Nakayama M, Uchiyama Y, Hirahara F, et al. The predictive value of biochemical markers of bone turnover for bone mineral density in ostmenopausal osteoporosis. J Bone Miner Res 2000;15(8):1537-44.
  • 24. Matsukawa N.Grzesik W.j.Tagahashi N, et al. The natriüretic peptide clearence reseptor lokally modulates the physiological effects of the natriuretic peptide systems. Proc Natl Acad 1999;96:7403-7408.
  • 25. Kajita M, Ezura Y, Iwasaki H, et al. Association of the -381T/C promoter variation of the brain natriuretic peptide gene with low bone-mineral density and rapid postmenopausal bone loss. J Hum Genet 2003;48(2):77-81.
  • 26. Nasu M, Sugimoto T, Chihara M, Hiraumi M, Kurimoto F, Chihara K. Effect of natural menopause on serum levels of IGF-I and IGFbinding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women. Eur J Endocrinol 1997;136(6):608- 616.
  • 27. López-Quiles J, Forteza-López A, Montiel M, Clemente C, Fernández-Tresguerres JA, Fernández-Tresguerres I. Effects of locally applied Insulin-like Growth Factor-I on osseointegration. Med Oral Patol Oral Cir Bucal. 2019;24(5):652-658.
  • 28. Ebeling PR, Jones JD, O’ fallon WM, et al. Short-term effects of recombinant human insulın-like growth factor I on bone turnover in normal women. J Clin Endocrinol Metab 1993;77:1384-1387.
  • 29. Reddi A. BMPs: from bone morphogenetic proteins to body morphogenetic proteins. Cytokine Growth Factor Rev 2005;16:249-250.
  • 30. Nasu M, Sugimoto T, Chihara M, Hiraumi M, Kurimoto F, Chihara K. Effect of natural menopause on serum levels of IGF-I and IGFbinding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women. Eur J Endocrinol 1997;136(6):608- 616.
  • 31. Nicolas V, Prewett A, Bettica P, et al. Age-related decreases in insulin-like growth factor-I and transforming growth factor-beta in femoral cortical bone from both men and women: implications for bone loss with aging. Clin Endocrinol Metab 1994 May;78(5):1009-10.
There are 31 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Makale
Authors

Mehmet Uçar 0000-0002-7064-8350

Hüseyin Demir 0000-0002-3890-7746

Publication Date April 1, 2022
Acceptance Date April 2, 2022
Published in Issue Year 2022 Volume: 7 Issue: 1

Cite

Vancouver Uçar M, Demir H. Deneysel Osteoporoz Oluşturulan Ratlarda Beyin Natriüretik Peptid Düzeyinin Biyokimyasal Belirteçler, Kemik Mineral Yoğunluğu ve Progenitör Faktörlerle İlişkisi. JAMER. 2022;7(1):5-12.