Therapeutic targets of osteoporosis: correlation of age, body mass index, blood glucose and blood lipids with sclerostin and DKK-1

doi:10.3969/j.issn.2095-4344.0395

Abstract

Abstract:

BACKGROUND: Chondrocytes have been shown to promote osteogenesis by inhibiting the expression of sclerostin. The key to regulating the balance between bone resorption and bone formation is sclerostin expression inhibition in the process of bone resorption.
OBJECTIVE: To analyze the correlation of age, body mass index, fasting blood glucose (FBG) and serum lipid with sclerostin and DKK-1 in adult men.
METHODS: Seventy healthy men aged 46-67 years who received physical examination were enrolled. Age, body height, body mass and medical history were collected. The FBG and blood lipids were detected. The serum levels of sclerostin and DKK-1 were detected by ELISA.
RESULTS AND CONCLUSION: (1) The level of sclerostin was significantly different among participants with different ages, body mass indices and FBG levels (P < 0.05). The serum level of DKK-1 in 57-67-year-old participants was significantly higher than that in 46-56-year-old participants (P < 0.05). (2) There was no relationship between serum sclerostin and DKK-1 levels. (3) Multiple linear regression analysis showed that serum level of sclerostin was significantly associated with FBG and body mass index. Serum level of DKK-1 was significantly associated with age. Therefore, much attention should be paid to age, FBG and body mass index in studies on sclerostin and DKK-1.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Bone and Bones, Metabolism, Body Mass Index, Blood Glucose, Osteoporosis, Tissue Engineering

CLC Number:

R318

Zhang Shu-dong1, Zhao Si-cong2, Li Shi-fei1, Zhou Jian1, Yao Qi1, 3. Therapeutic targets of osteoporosis: correlation of age, body mass index, blood glucose and blood lipids with sclerostin and DKK-1[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(32): 5085-5090.

Figures/Tables 2

References

[1] Balemans W, Ebeling M, Patel N, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001 1;10(5):537-543..

[2] Balemans W, Van Hul W. Human genetics of SOST. J Musculoskelet Neuronal Interact.2006;6(4):355-356.

[3] Brunkow M. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001;68(3):577-589.

[4] Delgado-Calle J, Sato A Y, Bellido T. Role and mechanism of action of sclerostin in bone. Bone.2016;96:29.

[5] Wu Y, Xu SY, Liu SY, et al. Upregulated serum sclerostin level in the T2DM patients with femur fracture inhibits the expression of bone formation/remodeling-associated biomarkers via antagonizing Wnt signaling. Eur Rev Med Pharmacol Sci. 2017;21(3):470-478.

[6] Behets GJ, Viaene L, Meijers B, et al. Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD.Plos One.2017;12(5):e0176411.

[7] Wei L, Guan L, Yan Z, et al. Sclerostin as a new key factor in vascular calcification in chronic kidney disease stages 3 and 4. Int Urol Nephrol. 2016;48(12):2043-2050.

[8] Shen J, Meyers CA, Shrestha S, et al. Sclerostin Expression in Skeletal Sarcomas. Human Pathology.2016;58:24-34.

[9] Hudson BD, Hum NR, Thomas CB, et al. SOST Inhibits Prostate Cancer Invasion. Plos One.2015;10(11):e0142058.

[10] Zhu M, Liu C, Li S, et al. Sclerostin induced tumor growth, bone metastasis and osteolysis in breast cancer. Sci Rep. 2017;7(1):11399.

[11] Ukita M, Yamaguchi T, Ohata N, et al. Sclerostin Enhances Adipocyte Differentiation in 3T3‐L1 Cells. J Cell Biochem. 2016;117(6): 1419-1428.

[12] Koide M, Kobayashi Y, Yamashita T, et al. Bone formation is coupled to resorption via suppression of sclerostin expression by osteoclasts. J Bone Miner Res. 2017;32(10):2074-2086.

[13] Menezes ME, Devine DJ, Shevde L A, et al. Dickkopf1: a tumor suppressor or metastasis promoter? Int J Cancer. 2012;130(7): 1477-1483.

[14] Tian J, Xu XJ, Shen L, et al. Association of Serum Dkk-1 Levels with β-catenin in Patients with Postmenopausal Osteoporosis. J Huazhong Univ Sci Technolog Med Sci. 2015;35(2):212-218.

[15] Xue J, Yang J, Yang L, et al. Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis. J Immunol Res. 2017;2017:6861575.

[16] Zarei A, Hulley PA, Sabokbar A, et al. Co-expression of DKK-1 and Sclerostin in Subchondral Bone of the Proximal Femoral Heads from Osteoarthritic Hips. Calcif Tissue Int.2017; 100(6):609-618.

[17] Shen L, Wu X, Tan J, et al. Combined detection of dickkopf-1 subtype classification autoantibodies as biomarkers for the diagnosis and prognosis of non-small cell lung cancer. Onco Targets Ther. 2017;10: 3545-3556.

[18] Cui R, Lin Z, Li Z, et al. Assessment risk of osteoporosis in Chinese people: relationship among body mass index, serum lipid profiles, blood glucose, and bone mineral density. Clin Interv Aging. 2016;11: 887-895.

[19] Pietrzyk B, Smertka M, Chudek J. Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders. Advances in clinical and experimental medicine. Adv Clin Exp Med. 2017;26(8):1283-1291.

[20] Xie W, Zhou L, Li S, et al. Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis. Ann N Y Acad Sci. 2016;1364: 25-31.

[21] Zimmerman Z F, Moon RT, Chien AJ. Targeting Wnt pathways in disease. Cold Spring Harb Perspect Biol. 2012;4(11). pii: a008086.

[22] Zhou Y, Wang T, Hamilton JL, et al. Wnt/β-catenin Signaling in Osteoarthritis and in Other Forms of Arthritis. Curr Rheumatol Rep. 2017 Sep;19(9):53.

[23] Coulson J, Bagley L, Barnouin Y, et al. Circulating levels of dickkopf-1, osteoprotegerin and sclerostin are higher in old compared with young men and women and positively associated with whole-body bone mineral density in older adults. Osteoporos Int. 2017;28(9):2683-2689.

[24] Bhattoa HP, Wamwaki J, Kalina E, et al. Serum sclerostin levels in healthy men over 50Â years of age. J Bone Miner Metab. 2013;31(5): 579-584.

[25] Amrein K, Amrein S, Drexler C, et al. Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults. J Clin Endocrinol Metab. 2012; 97(1):148-154.

[26] Gerber LM, Bener A, Alali HM, et al. Bone Mineral Density in Midlife Women: the Study of Women’s Health in Qatar. Climacteric. 2015; 18(2):316-322.

[27] Lloyd JT, Alley DE, Hawkes WG, et al. Body mass index is positively associated with bone mineral density in US older adults. Arch Osteoporos. 2014;9:175.

[28] Metzger TA, Schwaner SA, Laneve AJ, et al. Pressure and shear stress in trabecular bone marrow during whole bone loading. J Biomech. 2015;48(12):3035-3043.

[29] Yu O H Y, Richards B, Berger C, et al. The association between sclerostin and incident type 2 diabetes risk: a cohort study. Clin Endocrinol (Oxf). 2017;86(4):520-525.

[30] Tsentidis C, Gourgiotis D, Kossiva L, et al. Sclerostin distribution in children and adolescents with type 1 diabetes mellitus and correlation with bone metabolism and bone mineral density. Pediatric Diabetes. 2016;17(4):289-299.

[31] Hygum K, Starup-Linde J, Harsløf T, et al. MECHANISMS IN ENDOCRINOLOGY: Diabetes mellitus, a state of low bone turnover - a systematic review and meta-analysis. Eur J Endocrinol. 2017;176(3): R137-R157.

[32] Faienza M F, Ventura A, Delvecchio M, et al. High Sclerostin and Dickkopf-1 (DKK-1) Serum Levels in Children and Adolescents With Type 1 Diabetes Mellitus. J Clin Endocrinol Metab. 2017;102(4): 1174-1181.

[33] Sundararaghavan V, Mazur MM, Evans B, et al. Diabetes and bone health: latest evidence and clinical implications. Ther Adv Musculoskelet Dis. 2017;9(3):67-74.

[34] Wongdee K, Charoenphandhu N. Up date on type 2 diabetes-related osteoporosis. World J Diabetes. 2015;6(5):673-678.

[35] Cui LH, Shin MH, Chung EK, et al. Association between bone mineral densities and serum lipid profiles of pre- and post-menopausal rural women in South Korea. Osteoporos Int. 2005;16(12):1975-1981.

[36] Li S, Guo H, Liu Y, et al. Relationships of serum lipid profiles and bone mineral density in postmenopausal Chinese women. Clin Endocrinol (Oxf). 2015;82(1):53-58.

[37] Cosman F, Crittenden D B, Adachi J D, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;375(16):1532-1543.

[38] Recker R, Benson C, Matsumoto T, et al. A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density. J Bone Miner Res. 2015;30(2):216-24.

[39] Butler JS, Murray DW, Hurson CJ, et al. The role of Dkk1 in bone mass regulation: Correlating serum Dkk1 expression with bone mineral density. J Orthop Res. 2011;29(3):414-418.

[40] Dovjak P, Dorfer S, Kudlacek S, et al. Serum levels of sclerostin and dickkopf-1: effects of age, gender and fracture status.Gerontology. 2014;60(6):493-501.

[41] Hampson G, Edwards S, Conroy S, et al. The relationship between inhibitors of the Wnt signalling pathway (Dickkopf-1(DKK1) and sclerostin), bone mineral density, vascular calcification and arterial stiffness in post-menopausal women.Bone.2013;56(1):42-47.

[42] Glantschnig H, Hampton R A, Lu P, et al. Generation and selection of novel fully human monoclonal antibodies that neutralize Dickkopf-1 (DKK1) inhibitory function in vitro and increase bone mass in vivo. J Biol Chem. 2010;285(51):40135-40147.

[43] Goldstein S D, Matteo T, Bautista G W, et al. A monoclonal antibody against the Wnt signaling inhibitor dickkopf-1 inhibits osteosarcoma metastasis in a preclinical model. Oncotarget, 2016;7(16):21114-21123.

[44] Kato T, Khanh VC, Sato K, et al. Elevated expression of Dkk-1 by glucocorticoid treatment impairs bone regenerative capacity of adipose tissue-derived mesenchymal stem cells. Stem Cells Dev. 2018;27(2):85-99.

[45] Monica F, Kannan G, Marina S, et al. A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair. Nat Commun. 2016;7:11505.