Effect of Long Term Administration of Glucocorticoid to Bone Lining Cells Apoptosis (Gadis Meinar Sari) 251 THE EFFECT OF LONG TERM ADMINISTRATION OF GLUCOCORTICOID TO BONE LINING CELLS APOPTOSIS Gadis Meinar Sari Department of Physiology, Faculty of Medicine, Universitas Airlangga, Surabaya ABSTRAK Glukokortikoid banyak digunakan dalam pengobatan sistem kekebalan tubuh atau sebagai terapi peradangan. Namun pemberian jangka panjang dapat menyebabkan efek samping yang membahayakan jiwa. Salah satunya adalah hilangnya massa tulang yang meningkatkan risiko patah tulang. Bone lining cell yang berasal dari sel induk mesenchymal, berfungsi sebagai sel cadangan pembentuk osteoblas. Glukokortikoid bekerja langsung pada osteoblas, bila bone lining cell sel berkurang karena peningkatan apoptosis maka sel cadangan untuk pembentukan tulang akan menurun. Tujuan dari penelitian ini adalah untuk menghitung jumlah bone lining cell apoptosis setelah pemberian glukokortikoid jangka panjang. Penelitian ini menggunakan tikus putih Rattus norvegicus betina berusia 3 bulan yang dibagi menjadi 3 kelompok, setiap kelompok terdiri dari 7 ekor tikus. Kelompok tersebut adalah (1) kelompok kontrol; (2) kelompok perlakuan 1 diberi glukokortikoid 0,01 mg/hari; (3) kelompok perlakuan 2 diberi glukokortikoid 0,2 mg/hari. Perlakuan dilakukan selama 4 minggu dan pada akhir perlakuan tikus dikorbankan dan dilanjutkan dengan preparasi. Jumlah bone lining cell yang mengalami apoptosis dihitung melalui pemeriksaan jaringan tulang femur bagian metafisis menggunakan teknik imunohistokimia. Semua data dianalisis dengan analisis statistik Anova. Hasil penelitian menunjukkan bahwa jumlah bone lining cell apoptosis meningkat pada kelompok dengan pemberian glukokortikoid 0,01 mg/hari dan 0,2 mg/hari dibandingkan dengan kelompok kontrol dengan p = 0,000 (p <0,05). Jumlah bone lining cell apoptosis pada kelompok dosis glukokortikoid 0,2 mg/hari lebih tinggi daripada kelompok glukokortikoid dosis 0,01 mg/hari dengan p = 0,000 (p <0,05). Jadi, pemberian glukokortikoid jangka panjang meningkatkan apoptosis bone lining cell. (FMI 2016;52:251-257) Kata kunci: bone lining cell, apoptosis, glukokortikoid ABSTRACT Glucocorticoid is widely used in medical treatment as an immune system or an inflammation therapy. However its long term administration can cause life-threatening side effects. One of them is bone mass loss which increases the risk of bone fractures in the long-term use. Bone lining cells derived from mesenchymal stem cells, which serve as a backup cell bone-forming osteoblasts. Glucocorticoids acting directly on osteoblasts, bone lining cells when reduced due to increased apoptosis, the reserve cells to bone formation will be decreased. The aim of this study was to count the amount of apoptotic bone lining cells after long term glucocorticoid administration. This study used Rattus norvegicus females aged 3 months that were divided into 3 groups, each group consisted of 7 rats. The groups are: (1) control group; (2) treatment group 1 were given glucocorticoid 0.01 mg/day; (3) treatment group 2 were given glucocorticoid 0.2mg/day. The treatment carried out for 4 weeks and at the end of treatment, rats were sacrified and continued with preparation, and the number of bone lining cells that undergoing apoptosis was calculated through examination of the femur bone tissue metaphysis section using immunohistochemical technique. All data were analyzed with statistical analysis Anova. The result showed that the number of apoptotic bone lining cells increased in group with glucocorticoid administration 0.01 mg/day and 0.2 mg/day compared to control group with p = 0.000 (p <0.05). The number of apoptotic bone lining cells on the group of glucocorticoid dose 0.2 mg/day higher than the group of glucocorticoid dose 0.01 mg/day with p = 0.000 (p <0.05). In conclusion, long term glucocorticoid administration increase apoptosis of bone lining cells. (FMI 2016;52:251-257) Keywords: Bone lining cells, apoptosis, glucocorticoid Correspondence: Gadis Meinar Sari, Department of Physiology, Faculty of Medicine, Universitas Airlangga, Jl Mayjend Prof Dr Moestopo 47, Surabaya 60131. Ph0ne: +6231-503261. e-mail: sarigadis@yahoo.co.id INTRODUCTION Glucocorticoid is produced and secreted by adrenal gland in response to stress and regulates some tissue physiological processes. Among them, this hormone both brings about immunosuppression and anti- inflammation and influences apoptosis of some particular cells such as T-lymphocytes and monocytes. Due to its features, glucocorticoid is widely used in medical treatment as an immune system or an inflammation therapy. Glucocorticoid therapy can save many lives, however its long term administration can cause life-threatening side effects, one of them is bone mass loss which increases the risk of bone fractures (Adler 2003, Dvorak 2006).