Sains Malaysiana 47(11)(2018): 2731–2739

http://dx.doi.org/10.17576/jsm-2018-4711-16

 

The Effect of Palm Tocotrienol on Surface Osteoblast and Osteoclast in Excess Glucocorticoid Osteoporotic Rat Model

(Kesan Tokotrienol Sawit kepada Permukaan Osteoblas dan Osteoklas dalam Model Tikus Berlebihan Osteoporosis Glukokortikoid)

MOHAMAD FAIRUZ YAHAYA1*, AZIZI ZAINODIN1, REINUKAA PUPATHY1, EDWIN ONG HOCK MIN1, NURUL HUSNA ABU BAKAR1, NOR AZIMAH ZAMRI1, HALIM ISMAIL2 & ELVY SUHANA MOHD RAMLI1

 

1Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

 

2Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

 

Received: 20 March 2018/Accepted: 5 July 2018

 

ABSTRACT

A balanced interaction between osteoblast and osteoclast plays a major role in maintaining bone strength and structural integrity. Tocotrienol, a palm derivative with potent antioxidant properties showed an anti-osteoporotic effect but little is known about its mechanism of action. Hence, this research was conducted to determine the effects of palm tocotrienol on the surface osteoblast and osteoclast of the the glucocorticoid-induced osteoporotic bones. The study involved 40 male Sprague-Dawley rats weighing 250-300 g which were randomly divided into an equal number of Baseline, Sham, Adrx+Dexa (adrenalectomized with dexamethasone), Adrx+Dexa+ATF (adrenalectomized with dexamethasone supplemented with α-tocopherol) and Adrx+Dexa+PTT (adrenalectomized with dexamethasone supplemented with palm tocotrienol). Bloods were taken prior to sacrifice for serum biomarkers and either tibia or femur was harvested for bone biomarkers, gene expressions analysis and histological studies. A double-blinded experiment was performed to calculate the number of total cells (osteoblasts and osteoclast) with intact nuclei within five fields of view. While serum osteocalcin and gene expression did not show any changes, CTX level was increased in the Adrx+Dexa group but reduced after the supplementation of palm tocotrienol. Supplementation of palm tocotrienol also significantly decrease the osteoclast population (p<0.05) compared to Adrx+Dexa group. In contrast, osteoblast population showed no significant difference across the groups. The result showed that palm tocotrienol acts by modulating the osteoclasts but not osteoblast, which revert the dynamics of bone cells population in the osteoporotic bone to its pre-osteoporotic levels. Supplements of tocotrienol in daily diet may be beneficial in preventing osteoporosis.

 

Keywords: Antioxidant; osteoblast; osteoclast; osteoporosis; vitamin E

 

 

ABSTRAK

Interaksi seimbang antara osteoblas dan osteoklas memainkan peranan utama dalam mengekalkan kekuatan dan integriti struktur tulang. Tokotrienol, terbitan sawit dengan sifat antioksidan yang kuat telah menunjukkan kesan anti-osteoporosis tetapi amat sedikit diketahui tentang mekanisme tindakannya. Oleh yang demikian, kajian ini dijalankan untuk menentukan kesan tokotrienol sawit ke atas sel permukaan osteoblas dan osteoklas pada tulang osteoporosis aruhan glukokortikoid. Kajian ini melibatkan 40 ekor tikus Sprague-Dawley jantan dengan berat antara 250-300 g yang dibahagikan secara rawak kepada kumpulan Kawalan, Sham, Adrx+Dexa (adrenalektomi dengan deksamethason), Adrx+Dexa+ATF (adrenalektomi dengan deksamethason ditambah α-tokoferol) dan Adrx+Dexa+PTT (adrenalektomi dengan deksamethason ditambah tocotrienol sawit) secara oral selama dua bulan. Darah diambil daripada tikus sebelum dikorbankan dan tulang tibia atau femur kemudiannya diambil untuk kajian petanda biokimia dan histologi. Kajian ‘double blinded’ dilakukan dengan menghitung jumlah keseluruhan sel (osteoblas dan osteoklas) dengan nukleus dalam lima medan pandangan. Sementara serum osteokalsin dan ekspresi gen tidak menunjukkan sebarang perubahan, aras CTX meningkat pada kumpulan Adrx+Dexa tetapi menurun dengan suplementasi tocotrienol sawit. Suplementasi tocotrienol sawit juga menyebabkan penurunan ketara bilangan osteoklas (p<0.05) berbanding kumpulan Adrx+Dexa. Sebaliknya, populasi osteoblas tidak menunjukkan perbezaan yang signifikan pada kesemua kumpulan. Keputusan kajian menunjukkan bahawa tokotrienol sawit bertindak dengan memodulasi osteoklas tetapi bukan osteoblas yang mengembalikan dinamik osteoblas dan populasi osteoblas dalam tulang osteoporosis ke tahap pra-osteoporosis. Tambahan tokotrienol dalam diet harian mampu memberi manfaat dalam mencegah osteoporosis.

 

Kata kunci: Antioksidan; osteoblas; osteoklas; osteoporosis; vitamin E

REFERENCES

Abdul-Majeed Saif, Norazlina, M. & Ima-Nirwana Soelaiman. 2012. Effects of tocotrienol and lovastatin combination on osteoblast and osteoclast activity in estrogen-deficient osteoporosis. Evidence-Based Complementary and Alternative Medicine: ECAM 2012: 960742.

Aggarwal, B.B., Chitra Sundaram, Seema Prasad & Ramaswamy Kannappan. 2010. Tocotrienols, the vitamin E of the 21st century: It’s potential against cancer and other chronic diseases. Biochemical Pharmacology 80(11): 1613-1631.

Almeida, M., Li, H., Ambrogini, E., Weinstein, R.S. & Manolagas, S.C. 2011. Glucocorticoids and tumor necrosis factor α increase oxidative stress and suppress wnt protein signaling in osteoblasts. The Journal of Biological Chemistry 286(52): 44326-44335.

Boyle, W.J., Simonet, W.S. & Lacey, D.L. 2003. Osteoclast differentiation and activation. Nature 423(6937): 337-342.

Brooks, R., Kalia, P., Ireland, D.C., Beeton, C. & Rushton, N. 2011. Direct inhibition of osteoclast formation and activity by the vitamin E isomer gamma-tocotrienol. International Journal for Vitamin and Nutrition Research 81(6): 358-367.

Clarke, B. 2008. Normal bone anatomy and physiology. Clinical Journal of the American Society of Nephrology: CJASN 3 Suppl 3 (November): S131-S139.

Das, S., Lekli, I., Das, M., Szabo, G., Varadi, J., Juhasz, B., Bak, I., Nesaretam, K., Tosaki, A., Powell, S.R. & Das, D.K. 2008. Cardioprotection with palm oil tocotrienols: Comparison of different isomers. American Journal of Physiology-Heart and Circulatory Physiology 294(2): H970-H978.

De Nijs, R.N.J. 2008. Glucocorticoid-Induced osteoporosis: A review on pathophysiology and treatment options. Minerva Medica 99(1): 23-43.

Elvy Suhana Mohd Ramli, Ima Nirwana Soelaiman, Faizah Othman, Fairus Ahmad, Ahmad Nazrun Shuib, Norazlina Mohamed, Norliza Muhammad & Farihah Hj Suhaimi. 2012. The effects of Piper sarmentosum water extract on the expression and activity of 11β-hydroxysteroid dehydrogenase type 1 in the bones with excessive glucocorticoids. Iranian Journal of Medical Sciences 37(1): 39-46.

Fujita, K., Iwasaki, M., Ochi, H., Fukuda, T., Ma, C., Miyamoto, T., Takitani, K., Negishi-Koga, T., Sunamura, S., Kodama, T., Takayanagi, H., Tamai, H., Kato, S., Arai, H., Shinomiya, K., Itoh, H., Okawa, A., & Takeda, S. 2012. Vitamin E decreases bone mass by stimulating osteoclast fusion. Nature Medicine 18(4): 589-594.

Glaser, D.L. & Kaplan, F.S. 1997. Osteoporosis: Definition and clinical presentation. Spine 22(24): 12S-16S.

Ha, H.N., Lee, J-H., Kim, H-N. & Lee, Z.H. 2011. α-Tocotrienol inhibits osteoclastic bone resorption by suppressing RANKL expression and signaling and bone resorbing activity. Biochemical and Biophysical Research Communications 406(4): 546-551.

Jagtap, V.R., Ganu, J.V. & Nagane, N.S. 2011. BMD and serum intact osteocalcin in postmenopausal osteoporosis women. Indian Journal of Clinical Biochemistry 26(1): 70-73.

Khosla, S., Westendorf, J.J. & Oursler, M.J. 2008. Building bone to reverse osteoporosis and repair fractures. The Journal of Clinical Investigation 118(2): 421-428.

Leibbrandt, A. & Penninger, J.M. 2008. RANK/RANKL: Regulators of immune responses and bone physiology. Annals of the New York Academy of Sciences 1143: 123-150.

Lemaire, V., Tobin, F.L., Greller, L.D., Cho, C.R. & Suva, L.J. 2004. Modeling the Interactions between osteoblast and osteoclast activities in bone remodeling. Journal of Theoretical Biology 229(3): 293-309.

Maniam, S., Norazlina Mohamed, Ahmad Nazrun Shuid. & Ima Nirwana Soelaiman. 2008. Palm tocotrienol exerted better antioxidant activities in bone than alpha-tocopherol. Basic & Clinical Pharmacology & Toxicology 103(1): 55-60.

Manolagas, S.C. 2000. Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocrine Reviews 21(2): 115-137.

Marcus, R. 1996. Clinical Review 76: The nature of osteoporosis. The Journal of Clinical Endocrinology and Metabolism 81(1): 1-5.

Mitra, R. 2011. Adverse effects of corticosteroids on bone metabolism: A review. PM & R 3(5): 466-471.

Nazrun, A.S., Norazlina, M., Norliza, M. & Nirwana, S.I. 2012. The anti-inflammatory role of Vitamin E in prevention of osteoporosis. Advances in Pharmacological Sciences 2012: 142702.

Sen, C.K., Khanna, S. & Sashwati, R. 2006. Tocotrienols: Vitamin E beyond tocopherols. Life Sciences 78(18): 2088-2098.

Soelaiman, I.N., Wang Ming, Roshayati Abu Bakar., Nursyahrina, Atiqah Hashnan, Hanif Mohd Ali, Norazlina Mohamed., Norliza Muhammad & Ahmad Nazrun Shuid. 2012. Palm tocotrienol supplementation enhanced bone formation in oestrogen-deficient rats. International Journal of Endocrinology 2012: 532862.

Tan, B., Watson, R.R. & Preedy, V.R. 2012. Tocotrienols: Vitamin E Beyond Tocopherols. 2nd ed. Boca Raton: CRC Press.

Traber, M.G. 2007. Vitamin E regulatory mechanisms. Annual Review of Nutrition 27: 347-362.

 

*Corresponding author; email: mfairuzy@ukm.edu.my

 

 

 

 

 

 

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