Maternal uterin arter ligasyon modeli uygulanan fetal sıçanlarda kondrogenez ve osteogenezin Wnt/β-Catenin, S100 immünoekspresyon ve histomorfometri ile değerlendirilmesi
Öz
Amaç: Bu çalışmanın amacı, sıçanlarda maternal uterin arter ligasyonuna bağlı olarak gelişen intrauterine büyüme geriliğinde kondrogenez ve osteogenezin Wnt/β-catenin ve S100 ekspresyonlarının immünohistokimyasal ve histomorfometrik olarak değerlendirilmesi.
Gereç ve Yöntem: Gebe sıçanlar 3 gruba ayrıldı (n=5). Kontrol grubuna cerrahi veya anestezi uygulanmadı. Deney grubunda, 18. gebelik gününde bilateral maternal uterin arterlere ligasyon yapıldı. Sham grubuna uterin arter ligasyonu dışındaki tüm cerrahi işlem uygulandı. Fetuslar gebeliğin 20. gününde alındı, sol proksimal tibiadan büyüme plağı ve zonların kalınlıkları, trabeküler sayı ve kalınlıkları, kortikal kalınlıklar histomorfometrik olarak değerlendirildi. Büyüme plağında β-catenin ve S100 ekspresyonları immunohistokimyasal olarak değerlendirildi.
Bulgular: Deney grubunda büyüme plağı (p<0.01), proliferasyon zonu (p<0.05) ve dejenerasyon zonun kalınlıkları (p<0.01) belirgin olarak daha ince bulundu. Hipertrofik zonların kalınlığı daha az olarak ölçüldü (p>0.05). Aynı zamanda daha düşük sayıda trabekülar yapı (p<0.01) ve daha ince trabeküler kalınlık (p<0.05) bulundu. Deney grubunda β-catenin ekspresyonu daha düşük iken S100 ekspresyonunda artış saptandı.
Sonuç: Maternal uterin arter ligasyonuna bağlı fetal sıçan intrauterine büyüme geriliği modelinde, Wnt/β-catenin sinyal yolağındaki azalmaya bağlı olarak dejenere kemik yapısı ve büyüme plağında kısalmaya yol açmaktadır.
Anahtar Kelimeler
İntrauterine büyüme geriliği uterin arter ligasyonu büyüme plağı β-catenin S100 histomorfometri
Kaynakça
- Provot S, Schipani E. Fetal growth plate a developmental model of cellular adaptation to hypoxia. Ann N Y Acad Sci 2007; 1117: 26-39.
- Uysal A, Oktem G, Yılmaz Y, Uslu S, Aktug H, Yurtseven M. Quantitative immunohistochemical analysis of nitric oxide synthases and apoptosis regulator proteins in the fetal rat brain following maternal uterine artery ligation. Int J Neurosci 2008; 118 (6): 891-901.
- Ergaz Z, Avgil M, Ornoy A. Intrauterine growth restriction-etiology and consequences: what do we know about the human situation and experimental animal models? Reprod Toxicol. 2005; 20 (3): 301-22.
- Cetin I, Alvino G. Intrauterine growth restriction: Implications for placental metabolism and transport. A review. Placenta 2009; 30 (23): 77-82.
- Tomaszewska E, Dobrowolski P, Wydrych J. Postnatal administration of 2-oxoglutaric acid improves articular and growth plate cartilages and bone tissue morphology in pigs prenatally treated with dexamethasone. J Physiol Pharmacol 2012; 63 (5): 547-54.
- Vortkamp A, Pathi S, Peretti GM, Carusob E M, Zaleskeb D J, Tabina C J. Recapitulation of signals regulating embryonic bone formation during postnatal growth and in fracture repair. Mechanisms of Development 1998; 71 (1-2): 65-76.
- Erenpreisa J, Roach HI. Aberrations of cell cycle and cell death in normal development of the chick embryo growth plate. Mech Ageing Dev 1999; 108 (3): 227-38.
- DeLise AM, Fischer L, Tuan RS. Cellular interactions and signaling in cartilage development. Osteoarthritis and Cartilage 2000; 8 (5): 309-34.
- Tamamura Y, Otani T, Kanatani N et al. Developmental regulation of Wnt/β-catenin signals are required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem 2005; 280 (19): 19185-95.
- Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev 2002; 16 (12): 1446-65.
- Lee SH, Kim JY, Kim H et al. Amomum villosum induces longitudinal bone growth in adolescent female rats. J Tradit Chin Med 2012; 32 (3):453-8.
- Park H, Kong SY, Kim HW, Yang IH. Altered cellular kinetics in growth plate according to alterations in weight bearing. Yonsei Med J 2012; 53 (3): 618-24.
- Musumeci G, Castrogiovanni P, Loreto C, Castorina S, Pichler K, Weinberg A M. Post-traumatic caspase-3 expression in the adjacent areas of growth plate injury site: a morphological study. Int J Mol Sci 2013; 14 (8): 15767-84.
- Chen Y, Whetstone HC, Lin AC et al. Beta-catenin signaling plays a disparate role in different phases of fracture repair: Implications for therapy to improve bone healing. PloS Med 2007; 4 (7): e249.
- Agholme F, Aspenberg P. Wnt signaling and orthopedics, an overview. Acta Orthop 2011; 82 (2): 125-30.
- Lu C, Wan Y, Cao J et al. Wnt-mediated reciprocal regulation between cartilage and bone development during endochondral ossification. Bone 2013; 53 (2): 566-74.
- Uslu S, Oktem G, Uysal A, Soner BC, Arbak S, Ince U. Stem cell and extracellular matrix-related molecules increase following melatonin treatment in the skin of postmenopausal rats. Cell Biol Int 2014; 38 (8): 924-932.
- Moorer MC, Riddle RC. Regulation of Osteoblast Metabolism by Wnt Signaling. Endocrinol Metab 2018; 33 (3): 318-30.
- Leonardi R, Villari L, Bernasconi G, Piacentini C, Baciliero U, Travali S. Cellular S100 protein immunostaining in human dysfunctional temporomandibular joint discs. Arch Oral Biol 2000; 45 (5): 411-8.
- Aigner T, Neureiter D, Campean V, Soder S, Amann K. Expression of cartilage-specific markers in calcified and non-calcified atherosclerotic lesions. Atherosclerosis 2008; 196 (1): 37-41.
- Shia J, Klimstra DS, Li AR et al. Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma: an immunohistochemical and chromogenic in situ hybridization study. Mod Pathol 2005; 18 (10): 1350–6.
- Yanga Y, Fana X, Tao J et al. Impact of prenatal hypoxia on fetal bone growth and osteoporosis in ovariectomized offspring rats. Reprod Toxicol 2018; 78: 1–8.
- Ostergaard K, Andersen CB, Petersen J, Bendtzen K, Salter D. Validity of histopathological grading of articular cartilage from osteoarthritic knee joints. Ann Rheum Dis 1999; 58 (4): 208-13.
- Uslu S, Uysal A, Oktem G, Yurtseven M, Tanyalcın T, Basdemir G. Constructive effect of exogenous Melatonin against osteoporosis after ovariectomy in rats. Anal Quant Cytol Histol 2007; 29 (5): 317-25.
- Eriksson E, Zaman F, Chrysis D et al. Bortezomib Is Cytotoxic to the Human Growth Plate and Permanently Impairs Bone Growth in Young Mice. PLoS One 2012; 7 (11): e50523.
- Lui JC, Jee YH, Garrison P et al. Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions. PLoS Biol 2018; 23; 16 (7): e2005263.
- Oktem G, Uslu S, Vatansever SH, Aktug H, Yurtseven ME, Uysal A. Evaluation of the relationship between inducible nitric oxide synthase (INOS) activity and effects of melatonin in experimental osteoporosis in the rat. Surg Radio Anat 2006; 28: 157-62.
- He J, Niu Y, Wang F et al. Dietary curcumin supplementation attenuates inflammation, hepatic injury and oxidative damage in a rat model of intra-uterine growth retardation. Br J Nutr 2018; 120 (5): 537-48.
- Goodspeed D, Seferovic MD, Holland W et al. Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats. FASEB J 2015; 29 (3):807-19.
- Woodall SM, Breier BH, Johnston BM, Bassett NS, Barnard R, Gluckman PD. Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring. J Endocrinol 1999; 163 (1): 69-77.
- Bar-el Dadon S, Shahar R, Katalan V, Monsonego-Ornan E, Reifen R. Leptin administration affects growth and skeletal development in a rat intrauterine growth restriction model: Preliminary study. Nutrition 2011; 27 (9):973-7.
- Rauch F. Bone Growth in Length and Width: The Yin and Yang of Bone Stability. J Musculoskelet Neuronal Interact 2005; 5 (3): 194-201.
- Roach HI, Mehta G, Oreffo ROC, Clarke NMP, Cooper C. Temporal Analysis of Rat Growth Plates: Cessation of Growth with Age Despite Presence of a Physis. J Histochem Cytochem 2003; 51 (3): 373-83.
- Takano H, Aizawa T, Irie T, Itoi E, Kokubun S, Roach HI. Normal bone growth requires optimal estrogen levels: Negative effects of both high and low dose estrogen on the number of growth plate chondrocytes. Tohoku J Exp Med 2008; 214 (3): 269-80.
- Kanczler JM, Oreffo RO. Osteogenesis and angiogenesis: The potential for engineering bone. Eur Cell Mater 2008; 15: 100-14.
- Moore ER, Jacobs CR. The primary cilium as a signaling nexus for growth plate function and subsequent skeletal development. J Orthop Res 2018; 36 (2): 533-45.
- Golovchenko S, Hattori T, Hartmann C et al. Deletion of beta catenin in hypertrophic growth plate chondrocytes impairs trabecular bone formation. Bone 2013; 55 (1): 102-12.
- Burdan F, Szumilo J, Korobowicz A et al. Morphology and physiology of the epiphyseal growth plate. Folia Histochem Cytobiol 2009; 47 (1): 5-16.
- Candela ME, Cantley L, Yasuaha R, Iwamoto M, Pacifici M, Enomoto-Iwamoto M. Distribution of slow-cycling cells in epiphyseal cartilage and requirement of β-catenin signaling for their maintenance in growth plate. J Orthop Res 2014; 32 (5): 661-8.
- Papathanasiou I, Malizos KN, Tsezou A. Bone morphogenetic protein-2-induced Wnt/β-catenin signaling pathway activation through enhanced low-density-lipoprotein receptor-related protein 5 catabolic activity contributes to hypertrophy in osteoarthritic chondrocytes. Arthritis Res Ther 2012; 14 (2): R82.
- Moskalewski S, Hyc A, Jankowska-Steifer E, Osiecka-Iwan A. Formation of synovial joints and articular cartilage. Folia Morphol (Warsz) 2013; 72 (3): 181-7.
- Kubota T, Michigami T, Ozono K. Wnt Signaling in Bone. Clin Pediatr Endocrinol 2010; 19 (3):49-56.
- Yammani RR. S100 proteins in cartilage: Role in arthritis. Biochim Biophys Acta 2012; 1822 (4):600-6.
Evaluation of chondrogenesis and osteogenesis via Wnt/β-Catenin, S100 immunoexpression and histomorphometry in fetal rats following maternal uterine artery ligation
Öz
Aim: The aim of this study is to investigate the effects of intrauterine growth retardation depending on maternal uterine artery ligation, Wnt/β-catenin and S100 expression immunohistochemistry and histomorphometrically on chondrogenesis and osteogenesis of fetal rats.
Materials and Methods: Maternal rats were randomly divided into 3 groups (n=5). No surgery or anesthesia were applied in control group. Bilaterally the maternal uterine arteries were ligated on gestational day 18 in experimental group. Although all surgical procedures were performed in sham group, the uterine artery ligation were not made. Fetuses were taken on gestational day 20, thicknesses of growth plate and zones, trabecular number and thickness and cortical thickness were evaluated with the histomorphometrically in samples from left proximal tibia. The expressions of β-catenin and S100 immunohistochemically were evaluated in the growth plate.
Results: Thicknesses of growth plate (p<0.01), proliferation zone (p<0.05) and degeneration zone (p<0.01) were measured significantly thinner in experimental group than the others and thicknesses of hypertrophic zones were lesser than the control and sham group, but the results were not statistically significant (p>0.05). Also trabecular numbers were lower (p<0.01) and trabecular thickness were also thinner (p<0.05) in experimental group. Expression of β-catenin was declined and S100 expression was increased in experimental group.
Conclusion: We conclude that maternal uterine artery ligation, leads to shortness of growth plate and degenerated bone architecture because of Wnt/β-catenin signaling pathway.
Anahtar Kelimeler
Intrauterine growth retardation uterine artery ligation growth plate β-catenin S100 histomorphometry
Kaynakça
- Provot S, Schipani E. Fetal growth plate a developmental model of cellular adaptation to hypoxia. Ann N Y Acad Sci 2007; 1117: 26-39.
- Uysal A, Oktem G, Yılmaz Y, Uslu S, Aktug H, Yurtseven M. Quantitative immunohistochemical analysis of nitric oxide synthases and apoptosis regulator proteins in the fetal rat brain following maternal uterine artery ligation. Int J Neurosci 2008; 118 (6): 891-901.
- Ergaz Z, Avgil M, Ornoy A. Intrauterine growth restriction-etiology and consequences: what do we know about the human situation and experimental animal models? Reprod Toxicol. 2005; 20 (3): 301-22.
- Cetin I, Alvino G. Intrauterine growth restriction: Implications for placental metabolism and transport. A review. Placenta 2009; 30 (23): 77-82.
- Tomaszewska E, Dobrowolski P, Wydrych J. Postnatal administration of 2-oxoglutaric acid improves articular and growth plate cartilages and bone tissue morphology in pigs prenatally treated with dexamethasone. J Physiol Pharmacol 2012; 63 (5): 547-54.
- Vortkamp A, Pathi S, Peretti GM, Carusob E M, Zaleskeb D J, Tabina C J. Recapitulation of signals regulating embryonic bone formation during postnatal growth and in fracture repair. Mechanisms of Development 1998; 71 (1-2): 65-76.
- Erenpreisa J, Roach HI. Aberrations of cell cycle and cell death in normal development of the chick embryo growth plate. Mech Ageing Dev 1999; 108 (3): 227-38.
- DeLise AM, Fischer L, Tuan RS. Cellular interactions and signaling in cartilage development. Osteoarthritis and Cartilage 2000; 8 (5): 309-34.
- Tamamura Y, Otani T, Kanatani N et al. Developmental regulation of Wnt/β-catenin signals are required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem 2005; 280 (19): 19185-95.
- Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev 2002; 16 (12): 1446-65.
- Lee SH, Kim JY, Kim H et al. Amomum villosum induces longitudinal bone growth in adolescent female rats. J Tradit Chin Med 2012; 32 (3):453-8.
- Park H, Kong SY, Kim HW, Yang IH. Altered cellular kinetics in growth plate according to alterations in weight bearing. Yonsei Med J 2012; 53 (3): 618-24.
- Musumeci G, Castrogiovanni P, Loreto C, Castorina S, Pichler K, Weinberg A M. Post-traumatic caspase-3 expression in the adjacent areas of growth plate injury site: a morphological study. Int J Mol Sci 2013; 14 (8): 15767-84.
- Chen Y, Whetstone HC, Lin AC et al. Beta-catenin signaling plays a disparate role in different phases of fracture repair: Implications for therapy to improve bone healing. PloS Med 2007; 4 (7): e249.
- Agholme F, Aspenberg P. Wnt signaling and orthopedics, an overview. Acta Orthop 2011; 82 (2): 125-30.
- Lu C, Wan Y, Cao J et al. Wnt-mediated reciprocal regulation between cartilage and bone development during endochondral ossification. Bone 2013; 53 (2): 566-74.
- Uslu S, Oktem G, Uysal A, Soner BC, Arbak S, Ince U. Stem cell and extracellular matrix-related molecules increase following melatonin treatment in the skin of postmenopausal rats. Cell Biol Int 2014; 38 (8): 924-932.
- Moorer MC, Riddle RC. Regulation of Osteoblast Metabolism by Wnt Signaling. Endocrinol Metab 2018; 33 (3): 318-30.
- Leonardi R, Villari L, Bernasconi G, Piacentini C, Baciliero U, Travali S. Cellular S100 protein immunostaining in human dysfunctional temporomandibular joint discs. Arch Oral Biol 2000; 45 (5): 411-8.
- Aigner T, Neureiter D, Campean V, Soder S, Amann K. Expression of cartilage-specific markers in calcified and non-calcified atherosclerotic lesions. Atherosclerosis 2008; 196 (1): 37-41.
- Shia J, Klimstra DS, Li AR et al. Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma: an immunohistochemical and chromogenic in situ hybridization study. Mod Pathol 2005; 18 (10): 1350–6.
- Yanga Y, Fana X, Tao J et al. Impact of prenatal hypoxia on fetal bone growth and osteoporosis in ovariectomized offspring rats. Reprod Toxicol 2018; 78: 1–8.
- Ostergaard K, Andersen CB, Petersen J, Bendtzen K, Salter D. Validity of histopathological grading of articular cartilage from osteoarthritic knee joints. Ann Rheum Dis 1999; 58 (4): 208-13.
- Uslu S, Uysal A, Oktem G, Yurtseven M, Tanyalcın T, Basdemir G. Constructive effect of exogenous Melatonin against osteoporosis after ovariectomy in rats. Anal Quant Cytol Histol 2007; 29 (5): 317-25.
- Eriksson E, Zaman F, Chrysis D et al. Bortezomib Is Cytotoxic to the Human Growth Plate and Permanently Impairs Bone Growth in Young Mice. PLoS One 2012; 7 (11): e50523.
- Lui JC, Jee YH, Garrison P et al. Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions. PLoS Biol 2018; 23; 16 (7): e2005263.
- Oktem G, Uslu S, Vatansever SH, Aktug H, Yurtseven ME, Uysal A. Evaluation of the relationship between inducible nitric oxide synthase (INOS) activity and effects of melatonin in experimental osteoporosis in the rat. Surg Radio Anat 2006; 28: 157-62.
- He J, Niu Y, Wang F et al. Dietary curcumin supplementation attenuates inflammation, hepatic injury and oxidative damage in a rat model of intra-uterine growth retardation. Br J Nutr 2018; 120 (5): 537-48.
- Goodspeed D, Seferovic MD, Holland W et al. Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats. FASEB J 2015; 29 (3):807-19.
- Woodall SM, Breier BH, Johnston BM, Bassett NS, Barnard R, Gluckman PD. Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring. J Endocrinol 1999; 163 (1): 69-77.
- Bar-el Dadon S, Shahar R, Katalan V, Monsonego-Ornan E, Reifen R. Leptin administration affects growth and skeletal development in a rat intrauterine growth restriction model: Preliminary study. Nutrition 2011; 27 (9):973-7.
- Rauch F. Bone Growth in Length and Width: The Yin and Yang of Bone Stability. J Musculoskelet Neuronal Interact 2005; 5 (3): 194-201.
- Roach HI, Mehta G, Oreffo ROC, Clarke NMP, Cooper C. Temporal Analysis of Rat Growth Plates: Cessation of Growth with Age Despite Presence of a Physis. J Histochem Cytochem 2003; 51 (3): 373-83.
- Takano H, Aizawa T, Irie T, Itoi E, Kokubun S, Roach HI. Normal bone growth requires optimal estrogen levels: Negative effects of both high and low dose estrogen on the number of growth plate chondrocytes. Tohoku J Exp Med 2008; 214 (3): 269-80.
- Kanczler JM, Oreffo RO. Osteogenesis and angiogenesis: The potential for engineering bone. Eur Cell Mater 2008; 15: 100-14.
- Moore ER, Jacobs CR. The primary cilium as a signaling nexus for growth plate function and subsequent skeletal development. J Orthop Res 2018; 36 (2): 533-45.
- Golovchenko S, Hattori T, Hartmann C et al. Deletion of beta catenin in hypertrophic growth plate chondrocytes impairs trabecular bone formation. Bone 2013; 55 (1): 102-12.
- Burdan F, Szumilo J, Korobowicz A et al. Morphology and physiology of the epiphyseal growth plate. Folia Histochem Cytobiol 2009; 47 (1): 5-16.
- Candela ME, Cantley L, Yasuaha R, Iwamoto M, Pacifici M, Enomoto-Iwamoto M. Distribution of slow-cycling cells in epiphyseal cartilage and requirement of β-catenin signaling for their maintenance in growth plate. J Orthop Res 2014; 32 (5): 661-8.
- Papathanasiou I, Malizos KN, Tsezou A. Bone morphogenetic protein-2-induced Wnt/β-catenin signaling pathway activation through enhanced low-density-lipoprotein receptor-related protein 5 catabolic activity contributes to hypertrophy in osteoarthritic chondrocytes. Arthritis Res Ther 2012; 14 (2): R82.
- Moskalewski S, Hyc A, Jankowska-Steifer E, Osiecka-Iwan A. Formation of synovial joints and articular cartilage. Folia Morphol (Warsz) 2013; 72 (3): 181-7.
- Kubota T, Michigami T, Ozono K. Wnt Signaling in Bone. Clin Pediatr Endocrinol 2010; 19 (3):49-56.
- Yammani RR. S100 proteins in cartilage: Role in arthritis. Biochim Biophys Acta 2012; 1822 (4):600-6.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 13 Mart 2020 |
| Gönderilme Tarihi | 28 Aralık 2018 |
| Yayımlandığı Sayı | Yıl 2020Cilt: 59 Sayı: 1 |
