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Journal of Integrative Agriculture  2022, Vol. 21 Issue (10): 3017-3025    DOI: 10.1016/j.jia.2022.07.037
Special Issue: 动物科学合辑Animal Science
Animal Science · Veterinary Medicine Advanced Online Publication | Current Issue | Archive | Adv Search |
Regulation of bone phosphorus retention and bone development possibly by BMP and MAPK signaling pathways in broilers
LIAO Xiu-dong1*, CAO Su-mei1, 3*, LI Ting-ting2, SHAO Yu-xin1, ZHANG Li-yang1, LU Lin1, ZHANG Ri-jun3, HOU Shui-sheng1, LUO Xu-gang2
1 Mineral Nutrition Research Division, State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R.China
2 Poultry Mineral Nutrition Laboratory, College of Animal Science and Technology, Yangzhou University, Yangzhou 225000, P.R.China
3 Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, P.R.China
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摘要  骨形态蛋白(bone morphogenetic protein,BMP)和促分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路在调控骨骼形成和发育中扮演着重要角色。然而,目前关于肉鸡饲粮不同非植酸磷水平(non-phytate phosphorus,NPP)对这些信号通路及其与骨磷沉积和骨骼发育相关性的影响尚不清楚。因此,本试验旨在研究饲粮添加磷对肉鸡BMP和MAPK信号通路及其与骨磷沉积和骨骼发育相关性的影响。将800只1日龄AA肉公鸡按体重随机分成5个处理组,每个处理组8个重复。5个处理组饲粮的NPP水平分别为:1-21日龄:0.15、0.25、0.35、0.45和0.55%,22-42日龄:0.15、0.22、0.29、0.36和0.43%。试验结果表明,随着饲粮NPP水平的增加,14和28日龄肉鸡胫骨细胞外信号调节激酶1(Extracellular Signal-Regulated Kinase 1,ERK1)的mRNA表达、14日龄肉鸡胫骨磷酸化ERK1及28和42日龄肉鸡胫骨BMP2的蛋白表达线性降低(P<0.04),而42日龄肉鸡胫骨c-Jun氨基末端激酶1(c-Jun N-terminal kinase 1,JNK1)的mRNA表达线性增加(P<0.02)。在14日龄,肉鸡胫骨灰分总磷沉积量、骨矿物质含量、骨密度、骨强度及胫骨灰分与ERK1JNK1 mRNA表达及磷酸化ERK1呈显著负相关(r=-0.726~-0.359,P<0.05),而胫骨碱性磷酸酶活性和骨钙素含量与ERK1 mRNA表达及磷酸化ERK1呈显著正相关(r=0.405~0.665,P<0.01)。在28日龄,肉鸡的胫骨灰分总磷沉积量、骨矿物质含量、骨密度、骨强度及胫骨灰分与ERK1 mRNA表达和BMP2蛋白表达呈显著负相关(r=-0.518~-0.370,P<0.05),而与胫骨碱性磷酸酶呈显著正相关(r=0.382~0.648,P<0.05)。结果表明,ERK1JNK1 mRNA表达、BMP2蛋白表达及磷酸化ERK1与胫骨灰分总磷沉积量、骨矿物质含量、骨密度、骨强度及胫骨灰分呈显著负相关,但是与胫骨碱性磷酸酶活性和骨钙素呈显著正相关,表明肉鸡骨磷沉积和骨骼发育受BMP和MAPK信号通路的调节。本研究揭示了肉鸡骨磷沉积和骨骼发育受BMP和MAPK信号通路调节的机制。

Abstract  

The bone morphogenetic protein (BMP) and mitogen-activated protein kinase (MAPK) signaling pathways play an important role in regulation of bone formation and development, however, it remains unclear that the effect of dietary different levels of non-phytate phosphorus (NPP) on these signaling pathways and their correlations with bone phosphorus (P) retention and bone development in broilers.  Therefore, this experiment was conducted to investigate the effect of dietary P supplementation on BMP and MAPK signaling pathways and their correlations with bone P retention and bone development in broilers.  A total of 800 one-day-old Arbor Acres male broilers were randomly allotted to 1 of 5 treatments with 8 replicates in a completely randomized design.  The 5 treatments of dietary NPP levels were 0.15, 0.25, 0.35, 0.45 and 0.55% or 0.15, 0.22, 0.29, 0.36 and 0.43% for broilers from 1 to 21 days of age or 22 to 42 days of age, respectively.  The results showed that extracellular signal-regulated kinase 1 (ERK1) mRNA expression in the tibia of broilers on days 14 and 28, phosphorylated-ERK1 (p-ERK1) on day 14, and BMP2 protein expression on days 28 and 42 decreased linearly (P<0.04), while c-Jun N-terminal kinase 1 (JNK1) mRNA expression on day 42 increased linearly (P<0.02) with the increase of dietary NPP level.  At 14 days of age, total P accumulation in tibia ash (TPTA), bone mineral concentration (BMC), bone mineral density (BMD), bone breaking strength (BBS) and tibia ash were negatively correlated (r=–0.726 to –0.359, P<0.05) with ERK1 and JNK1 mRNA as well as p-ERK1; tibia alkaline phosphatase (ALP) and bone gal protein (BGP) were positively correlated (r=0.405 to 0.665, P<0.01) with ERK1 mRNA and p-ERK1.  At 28 days of age, TPTA, BMC, BMD, BBS and tibia ash were negatively correlated (r=–0.518 to –0.370, P<0.05) with ERK1 mRNA and BMP2 protein, while tibia ALP was positively correlated (r=0.382 to 0.648, P<0.05) with them.  The results indicated that TPTA, BMC, BMD, BBS or tibia ash had negative correlations, while tibia ALP and BGP had positive correlations with ERK1 and JNK1 mRNAs, BMP2 protein and p-ERK1, suggesting that bone P retention and bone development might be regulated by BMP and MAPK signaling pathways in broiler chickens.

Keywords:  Broiler        bone development        bone phosphorus retention        signaling pathway  
Received: 09 June 2021   Accepted: 22 September 2021
Fund: The present study was supported by the Key Program of the National Natural Science Foundation of China (31630073), the China Agriculture Research System of MOF and MARA (CARS-41), and the Agricultural Science and Technology Innovation Program, China (ASTIP-IAS09).
About author:  LIAO Xiu-dong, Tel: +86-10-62820866, E-mail: liaoxd56@163.com; Correspondence LUO Xu-gang, E-mail: wlysz@263.net * These authors contributed equally to this study.

Cite this article: 

LIAO Xiu-dong, CAO Su-mei, LI Ting-ting, SHAO Yu-xin, ZHANG Li-yang, LU Lin, ZHANG Ri-jun, HOU Shui-sheng, LUO Xu-gang. 2022. Regulation of bone phosphorus retention and bone development possibly by BMP and MAPK signaling pathways in broilers. Journal of Integrative Agriculture, 21(10): 3017-3025.

Beck G R, Knecht N. 2003. Osteopontin regulation by inorganic phosphate is ERK1/2-, protein kinase C-, and proteasome-dependent. Journal of Biological Chemistry, 278, 41921–41929.
Beck L, Sitara D. 2019. Animal models of phosphorus homeostasis. Current Molecular Biology Reports, 5, 34–47.
Bergwitz C, Jüppner H. 2010. Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annual review of medicine, 61, 91–104.
Berndt T, Kumar R. 2009. Novel mechanisms in the regulation of phosphorus homeostasis. Physiology (Bethesda), 24, 17–25.
Cao S M, Li T T, Shao Y X, Zhang L Y, Lu L, Zhang R J, Hou S S, Luo X G, Liao X D. 2021. Regulation of bone phosphorus retention and bone development possibly by related hormones and local bone-derived regulators in broiler chicks. Journal of Animal Science and Biotechnology, 12, 88.
Ge C X, Xiao G Z, Jiang D, Franceschi R T. 2007. Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development. Journal of Cell Biology, 176, 709–718.
Goretti Penido M, Alon U S. 2012. Phosphate homeostasis and its role in bone health. Pediatric nephrology, 27, 2039–2048. 
Greenblatt M B, Shim J H, Glimcher L H. 2013. Mitogen-activated protein kinase pathways in osteoblasts. Annual Review of Cell and Developmental Biology, 29, 63–79.
Greenblatt M B, Shim J H, Zou W G, Sitara D, Schweitzer M, Hu D, Lotinun S, Sano Y, Baron R, Park J M, Arthur S, Xie M, Schneider M D, Zhai B, Gygi S, Davis R, Glimcher L H. 2010. The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice. The Journal of Clinical Investigation, 120, 2457–2473.
Hansen N M, Felix R, Bisaz S. 1976. Aggregation of hydroxyapatite crystals. Biochimica et biophysica acta, 451, 549–559.
Heaney R P. 2004. Phosphorus nutrition and the treatment of osteoporosis. Mayo Clinic Proceedings, 79, 91–97.
Huang R L, Yuan Y, Tu J, Zou G M, Li Q. 2014. Opposing TNF-α/IL-1β- and BMP-2-activated MAPK signaling pathways converge on Runx2 to regulate BMP-2-induced osteoblastic differentiation. Cell death and disease, 17, e1187.
Kim J M, Yang Y S, Park K H, Oh H, Greenblatt M B, Shim J H. 2019. The ERK MAPK pathway is essential for skeletal development and homeostasis. International Journal of Molecular Sciences, 20, 1803.
Kono S J, Oshima Y, Hoshi K, Bonewald L F, Oda H, Nakamura K, Kawaguchi H, Tanaka S. 2007. Erk pathways negatively regulate matrix mineralization. Bone, 40, 68–74.
Li S F, Lu L, Liao X D, Gao T Q, Wang F N, Zhang L Y, Xi L, Liu S B, Luo X G. 2016. Manganese elevates manganese superoxide dismutase protein level through protein kinase C and protein tyrosine kinase. Biometals, 29, 265–274.
Li Z, Oh H, Cung M, Marquez S J, Sun J, Hammad H, Janssens S, Pouliot P, Lambrecht B N, Yang Y S, Shim J H, Greenblatt M B. 2020. TAOK3 is a MAP3K contributing to osteoblast differentiation and skeletal mineralization. Biochemical and Biophysical Research Communications, 531, 497–502.
Livak K J, Schmittgen T D. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(–Delta Delta C) method. Methods, 25, 402–408.
Magne D, Bluteau G, Faucheux C, Palmer G, Vignes-colombeix C, Pilet P, Rouillon T, Caverzasio J, Weiss P, Daculsi G, Guicheux J. 2003. Phosphate is a specific signal for ATDC5 chondrocyte maturation and apoptosis-associated mineralization: Possible implication of apoptosis in the regulation of endochondral ossification. Journal of bone and Mineral Research, 18, 1430–1442.
Massagué J, Wotton D. 2000. Transcriptional control by the TGF beta/Smad signaling system. EMBO Journal, 19, 1745–1754.
Nishino J, Yamazaki M, Kawai M, Tachikawa K, Yamamoto K, Miyagawa K, Kogo M, Ozono k, Michigami T. 2017. Extracellular phosphate induces the expression of dentin matrix protein 1 through the FGF receptor in osteoblasts. Journal of Cellular Biochemistry, 118, 1151–1163.
NRC (National Research Council). 1994. Nutrient Requirements of Poultry. 9th ed. National Academies Press, Washington, D.C. 
Phimphilai M, Zhoa Z R, Boules H, Roca H, Franceschi R T. 2006. BMP signaling is required for RUNX2-dependent induction of the osteoblast phenotype. Journal of Bone and Mineral Research, 21, 637–646.
Proszkowiec W M, Angel R. 2013. Calcium and phosphorus metabolism in broilers: Effect of homeostatic mechanism on calcium and phosphorus digestibility. The Journal of Applied Poultry Research, 22, 609–627.
Quarles L D. 2003. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. American Journal of Physiology Endocrinology and metabolism, 285, E1–E9.
Rao S V R, Raju M V L N, Paul S S, Prakash B. 2019. Effect of supplementing graded concentrations of non-phytate phosphorus on performance, egg quality and bone mineral variables in White Leghorn layers. British Poultry Science, 60, 56–63.
Rawadi G, Vayssiere B, Dunn F, Baron R, Roman-Roman S. 2003. BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop. Journal of Bone and Mineral Research, 18, 1842–1853.
Sanchez-Rodriguez E, Benavides-Reyes C, Torres C, Dominguez-Gasca N, Garcia-Ruiz A I, Gonzalez-Lopez S, Rodriguez-Navarro A B. 2019. Changes with age (from 0 to 37 D) in tibiae bone mineralization, chemical composition and structural organization in broiler chickens. poultry science, 98, 5215–5225.
Shao Y X, Sun G M, Cao S M, Lu L, Zhang L Y, Liao X D, Luo X G. 2019. Bone phosphorus retention and bone development of broilers at different ages. poultry science, 98, 2114–2121.
Shapiro R, Heaney R P. 2003. Co-dependence of calcium and phosphorus for growth and bone development under conditions of varying deficiency. Bone, 32, 532–540.
Steel R G D, Torrie J H. 1980. Principles and Procedures of Statistics: A Biometrical Approach. 2nd. McGraw-Hill, New York. p. 633.
Thorp B H. 1994. Skeletal disorders in the fowl: A review. Avian pathology, 23, 203–236.
Wei Q S, He M C, Chen M H, Chen Z Q, Yang F, Wang H B, Zhang J, He W. 2017. Icariin stimulates osteogenic differentiation of rat bone marrow stromal stem cells by increasing TAZ expression. Biomedicine & Pharmacotherapy, 91, 581–589.
Williams B, Solomon D, Waddington D, Thorp B, Farquharson C. 2000. Skeletal development in the meat-type chicken. British Poultry Science, 41, 141–149.
Wozney J M, Rosen V. 1998. Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clinical orthopaedics and Related Research, 346, 26–37.
Xiao G Z, Gopalakrishnan R, Jiang D, Reith E, Benson M D, Franceschi R T. 2002. Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. Journal of Bone and Mineral Research, 17, 101–110.
Xiao G Z, Jiang D, Thomas P, Benson M D, Guan K L, Karsenty G, Franceschi R T. 2000. MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. Journal of Biological Chemistry, 275, 4453–4459.
Zhang Z W, Wang J D, Lü X Y. 2014. An integrated study of natural hydroxyapatite-induced osteogenic differentiation of mesenchymal stem cells using transcriptomics, proteomics and microRNA analyses. Biomedical Materials, 9, 045005
Zur Nieden N I, Kempka G, Ahr H J. 2003. In vitro differentiation of embryonic stem cells into mineralized osteoblasts. Differentiation, 71, 18–27.

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