Bone and Bone Marrow Pro-osteoclastogenic Cytokines Are Up-regulated in Osteoporosis Fragility Fractures

Overview

Journal Osteoporos Int

Specialties Endocrinology
Orthopedics

Date 2010 Dec 1

PMID 21116815

Citations 21

Authors

P DAmelio

I Roato

L DAmico

L Veneziano

E Suman

F Sassi

G Bisignano

R Ferracini

G Gargiulo

F Castoldi

G P Pescarmona

G C Isaia

Affiliations

Soon will be listed here.

Abstract

Unlabelled: This study evaluates cytokines production in bone and bone marrow of patients with an osteoporotic fracture or with osteoarthritis by real time PCR, Western blot and immunohistochemistry. We demonstrate that the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in patients with osteoporotic fractures.

Introduction: Fragility fractures are the resultant of low bone mass and poor bone architecture typical of osteoporosis. Cytokines involved in the control of bone cell maturation and function are produced by both bone itself and bone marrow cells, but the roles of these two sources in its control and the amounts they produce are not clear. This study compares their production in patients with an osteoporotic fracture and those with osteoarthritis.

Methods: We evaluated 52 femoral heads from women subjected to hip-joint replacement surgery for femoral neck fractures due to low-energy trauma (37), or for osteoarthritis (15). Total RNA was extracted from both bone and bone marrow, and quantitative PCR was used to identify the receptor activator of nuclear factor kB Ligand (RANKL), osteoprotegerin (OPG), macrophage colony stimulating factor (M-CSF), transforming growth factor β (TGFβ), Dickoppf-1 (DKK-1) and sclerostin (SOST) expression. Immunohistochemistry and Western blot were performed in order to quantify and localize in bone and bone marrow the cytokines.

Results: We found an increase of RANKL/OPG ratio, M-CSF, SOST and DKK-1 in fractured patients, whereas TGFβ was increased in osteoarthritic bone. Bone marrow produced greater amounts of RANKL, M-CSF and TGFβ compared to bone, whereas the production of DKK-1 and SOST was higher in bone.

Conclusions: We show that bone marrow cells produced the greater amount of pro-osteoclastogenic cytokines, whereas bone cells produced higher amount of osteoblast inhibitors in patients with fragility fracture, thus the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in these patients.

Citing Articles

Impact of Alcohol on Bone Health in People Living With HIV: Integrating Clinical Data From Serum Bone Markers With Morphometric Analysis in a Non-Human Primate Model.

Denys A, Norman A, Perrien D, Suva L, Simon L, McDaniel L JBMR Plus. 2023; 7(1):e10703.

PMID: 36699637 PMC: 9850440. DOI: 10.1002/jbm4.10703.

Male osteoporosis.

Bandeira L, Silva B, Bilezikian J Arch Endocrinol Metab. 2022; 66(5):739-747.

PMID: 36382763 PMC: 10118818. DOI: 10.20945/2359-3997000000563.

Bone physiological microenvironment and healing mechanism: Basis for future bone-tissue engineering scaffolds.

Zhu G, Zhang T, Chen M, Yao K, Huang X, Zhang B Bioact Mater. 2021; 6(11):4110-4140.

PMID: 33997497 PMC: 8091181. DOI: 10.1016/j.bioactmat.2021.03.043.

Assessment of Wnt pathway selected gene expression levels in peripheral blood mononuclear cells (PBMCs) of postmenopausal patients with low bone mass.

Stuss M, Migdalska-Sek M, Brzezianska-Lasota E, Michalska-Kasiczak M, Bazela P, Sewerynek E Bosn J Basic Med Sci. 2020; 21(4):461-470.

PMID: 33357212 PMC: 8292866. DOI: 10.17305/bjbms.2020.5179.

Bone Matrix Levels of Dickkopf and Sclerostin are Positively Correlated with Bone Mass and Strength in Postmenopausal Osteoporosis.

Ueland T, Stilgren L, Bollerslev J Int J Mol Sci. 2019; 20(12).

PMID: 31197079 PMC: 6627473. DOI: 10.3390/ijms20122896.

References

Marques-Pinheiro A, Levasseur R, Cormier C, Bonneau J, Boileau C, Varret M . Novel LRP5 gene mutation in a patient with osteoporosis-pseudoglioma syndrome. Joint Bone Spine. 2010; 77(2):151-3. DOI: 10.1016/j.jbspin.2009.11.013. View

DAmelio P, Cristofaro M, Grimaldi A, Ravazzoli M, Pluviano F, Grosso E . The role of circulating bone cell precursors in fracture healing. Calcif Tissue Int. 2010; 86(6):463-9. DOI: 10.1007/s00223-010-9362-3. View

Massague J . The transforming growth factor-beta family. Annu Rev Cell Biol. 1990; 6:597-641. DOI: 10.1146/annurev.cb.06.110190.003121. View

Macsai C, Foster B, Xian C . Roles of Wnt signalling in bone growth, remodelling, skeletal disorders and fracture repair. J Cell Physiol. 2008; 215(3):578-87. DOI: 10.1002/jcp.21342. View

Ohnaka K, Taniguchi H, Kawate H, Nawata H, Takayanagi R . Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts: novel mechanism of glucocorticoid-induced osteoporosis. Biochem Biophys Res Commun. 2004; 318(1):259-64. DOI: 10.1016/j.bbrc.2004.04.025. View

Frost M, Andersen T, Yadav V, Brixen K, Karsenty G, Kassem M . Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin. J Bone Miner Res. 2010; 25(3):673-5. DOI: 10.1002/jbmr.44. View

Appel H, Loddenkemper C, Miossec P . Rheumatoid arthritis and ankylosing spondylitis - pathology of acute inflammation. Clin Exp Rheumatol. 2009; 27(4 Suppl 55):S15-9. View

Meyer Jr R, Meyer M, Tenholder M, Wondracek S, Wasserman R, Garges P . Gene expression in older rats with delayed union of femoral fractures. J Bone Joint Surg Am. 2003; 85(7):1243-54. DOI: 10.2106/00004623-200307000-00010. View

Bostrom M . Expression of bone morphogenetic proteins in fracture healing. Clin Orthop Relat Res. 1999; (355 Suppl):S116-23. DOI: 10.1097/00003086-199810001-00013. View

10.

Leibbrandt A, Penninger J . RANK(L) as a key target for controlling bone loss. Adv Exp Med Biol. 2009; 647:130-45. DOI: 10.1007/978-0-387-89520-8_9. View

11.

Dobnig H, Hofbauer L, Viereck V, Obermayer-Pietsch B, Fahrleitner-Pammer A . Changes in the RANK ligand/osteoprotegerin system are correlated to changes in bone mineral density in bisphosphonate-treated osteoporotic patients. Osteoporos Int. 2006; 17(5):693-703. DOI: 10.1007/s00198-005-0035-4. View

12.

Lane N, Yao W . Glucocorticoid-induced bone fragility. Ann N Y Acad Sci. 2010; 1192:81-3. PMC: 4834043. DOI: 10.1111/j.1749-6632.2009.05228.x. View

13.

Leibbrandt A, Penninger J . RANKL/RANK as key factors for osteoclast development and bone loss in arthropathies. Adv Exp Med Biol. 2009; 649:100-13. DOI: 10.1007/978-1-4419-0298-6_7. View

14.

Ekman E . The role of the orthopaedic surgeon in minimizing mortality and morbidity associated with fragility fractures. J Am Acad Orthop Surg. 2010; 18(5):278-85. DOI: 10.5435/00124635-201005000-00004. View

15.

Bondeson J, Blom A, Wainwright S, Hughes C, Caterson B, van den Berg W . The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis. Arthritis Rheum. 2010; 62(3):647-57. DOI: 10.1002/art.27290. View

16.

DAmelio P, Grimaldi A, Di Bella S, Brianza S, Cristofaro M, Tamone C . Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone. 2008; 43(1):92-100. DOI: 10.1016/j.bone.2008.02.017. View

17.

Velasco J, Zarrabeitia M, Prieto J, Perez-Castrillon J, Perez-Aguilar M, Perez-Nunez M . Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study. Osteoporos Int. 2009; 21(1):109-18. DOI: 10.1007/s00198-009-0931-0. View

18.

Isaia G, Giorgino R, Rini G, Bevilacqua M, Maugeri D, Adami S . Prevalence of hypovitaminosis D in elderly women in Italy: clinical consequences and risk factors. Osteoporos Int. 2003; 14(7):577-82. DOI: 10.1007/s00198-003-1390-7. View

19.

Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle W, Lacey D, Riggs B . Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. 2003; 111(8):1221-30. PMC: 152939. DOI: 10.1172/JCI17215. View

20.

Appel H, Ruiz-Heiland G, Listing J, Zwerina J, Herrmann M, Mueller R . Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum. 2009; 60(11):3257-62. DOI: 10.1002/art.24888. View