Correlation of Serum CCL3/MIP-1α Levels with Disease Severity in Postmenopausal Osteoporotic Females

Year 2018, Volume: 35 Issue: 4, 320 - 325, 01.07.2018

Hui Wan Tie-yong Qian Xiao-jing Hu Ci-you Huang Wei-feng Yao

Abstract

Background: The pro-inflammatory protein chemokine cytokine ligand 3 is well established as a vital regulator of bone resorption and osteoclast stimulation. Aims: To investigate if serum cytokine ligand 3 levels correlated with disease severity in postmenopausal osteoporotic women.Study Design: Cross-sectional study.Methods: Eighty-two postmenopausal osteoporotic women, 76 postmenopausal non-osteoporotic women, and 80 healthy women of childbearing age were recruited. The total hip, femoral neck, and L1-L4 spine bone mineral density were assessed by dual-energy X-ray absorptiometry. Serum cytokine ligand 3 concentrations were examined using a commercial enzyme-linked immunosorbent assay kit. Serum inflammatory cytokine interleukin-6, tumor necrosis factor-alpha, and the bone metabolic markers, carboxy-terminal crosslinked and tartrate-resistant acid phosphatase 5b were also examined. Scores on both the visual analogue scale and the Oswestry Disability Index were utilized to assess clinical severity.Results: Patients in the postmenopausal osteoporotic group had significantly increased serum cytokine ligand 3 levels compared with those in both the postmenopausal non-osteoporotic group (40.9±15.1 pg/mL vs 24.2±8.7 pg/mL, p<0.001) and control group (40.9±15.1 pg/mL vs 23.9±9.1 pg/mL, p<0.001). Serum cytokine ligand 3 levels negatively correlated with bone mineral density at the total hip (r=-0.345, p=0.002), femoral neck (r=-0.329, p=0.003), and L1-L4 lumbar spine (r=-0.354, p=0.001) and positively correlated with visual analogue scale scores (r=0.413, p<0.001) and the Oswestry Disability Index (r=0.360, p<0.001). Moreover, serum cytokine ligand 3 levels were correlated with increased tumor necrosis factor-alpha (r=0.305, p=0.005), interleukin-6 (r=0.288, p=0.008), terminal crosslinked and tartrate-resistant acid phosphatase 5b (r=0.371, p<0.001), and carboxy-terminal crosslinked (r=0.317, p=0.004) levels. All correlations were still significant after adjusting for both body mass index and age. Conclusion: Chemokine cytokine ligand 3 may be a useful biomarker that can be used to predict disease severity of postmenopausal osteoporosis. Therapies targeting cytokine ligand 3 and its related signaling pathways to inhibit and delay the osteoclastogenesis process deserve further investigation.

Keywords

CCL3, Chemokine, osteoporosis, post-menopausal, severity

References

• 1. Black DM, Rosen CJ. Clinical Practice. Postmenopausal Osteoporosis. N Engl J Med 2016;374:254-62.
• 2. Pisani P, Renna MD, Conversano F, Casciaro E, Di Paola M, Quarta E, et al. Major osteoporotic fragility fractures: risk factor updates and societal impact. World J Orthop 2016;7:171-81.
• 3. Compston J. Osteoporosis: advances in risk assessment and management. Clin Med (Lond) 2016;16(Suppl 6):121-24.
• 4. Pietschmann P, Rauner M, Sipos W, Kerschan-Schindl K. Osteoporosis: an agerelated and gender-specific disease a mini-review. Gerontology 2009;55:3-12.
• 5. Abrahamsen B, van Staa T, Ariely R, Olson M, Cooper C. Excess mortality following hip fracture: a systematic epidemiological review. Osteoporos Int 2009;20:1633-50.
• 6. Chan CK, Mason A, Cooper C, Dennison E. Novel advances in the treatment of osteoporosis. Br Med Bull 2016;119:129-42.
• 7. Schweser KM, Crist BD. Osteoporosis: a discussion on the past 5 years. Curr Rev Musculoskelet Med 2017;10:265-74.
• 8. Fan YL, Peh WC. Radiology of Osteoporosis: Old and New Findings. Semin Musculoskelet Radiol 2016;20:235-45.
• 9. Shetty S, Kapoor N, Bondu JD, Thomas N, Paul TV. Bone turnover markers: Emerging tool in the management of osteoporosis. Indian J Endocrinol Metab 2016;20:846-52
• 10. Eastell R, Hannon RA. Biomarkers of bone health and osteoporosis risk. Proc Nutr Soc 2008;67:157-62.
• 11. Legler DF, Thelen M. Chemokines: Chemistry, Biochemistry and Biological Function. Chimia (Aarau) 2016;70:856-9.
• 12. Fu R, Liu H, Zhao S, Wang Y, Li L, Gao S, et al. Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease. Cancer Cell Int 2014;14:132.
• 13. Baba T, Mukaida N. Role of macrophage inflammatory protein (MIP)-1α/CCL3 in leukemogenesis. Mol Cell Oncol 2014;1:e29899.
• 14. Jämsen E, Kouri VP, Ainola M, Goodman SB, Nordström DC, Eklund KK, et al. Correlations between macrophage polarizing cytokines, inflammatory mediators, osteoclast activity, and toll-like receptors in tissues around aseptically loosened hip implants. J Biomed Mater Res A 2017;105:454-63.
• 15. Kawao N, Tamura Y, Horiuchi Y, Okumoto K, Yano M, Okada K, et al. The Tissue Fibrinolytic System Contributes to the Induction of Macrophage Function and CCL3 during Bone Repair in Mice. PLoS One 2015;10:e0123982.
• 16. Kukita T, Nomiyama H, Ohmoto Y, Kukita A, Shuto T, Hotokebuchi T, et al. Macrophage inflammatory protein-1 alpha (LD78) expressed in human bone marrow: its role in regulation of hematopoiesis and osteoclast recruitment. Lab Invest 1997;76:399-406.
• 17. Fu R, Liu H, Zhao S, Wang Y, Li L, Gao S, et al. Osteoblast inhibition by chemokine cytokine ligand3 in myeloma-induced bone disease. Cancer Cell Int 2014;14:132. 18. World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: report of a WHO Study Group. World Health Organ Tech Rep Ser 1994;843:1-129.