The Role of Myeloma Cells to Osteoclast Activation

(1)

The Role of Myeloma Cells to Osteoclast Activation

Bahareh Sadeghi, M.Sc.1_{, Saeid Abroun, Ph.D.}1_{*, Behzad Poopak, Ph.D.}2_,

Abbas Hajfathali, M.D.3_{, Najmeddin Saki, M.Sc.}1_,_{Najmeh Vaghef, M.Sc.}1

1. Hematology Department, Faculty of Medical Science, Tarbiat Modarres University, Tehran, Iran 2. Hematology Department, Islamic Azad University, Tehran Medical Branch, Tehran, Iran 3. Hematology and Oncology Department, Shahid Beheshti Medical Sciences University, Tehran, Iran

* Corresponding Address: P.O.Box: 14115-331, Hematology Department, Faculty of Medical Science, Tarbiat Modarres University, Tehran, Iran

Email: abroun@modares.ac.ir

Received: 21/Jun/2010, Accepted: 20/Sep/2010 Abstract

Objective: Multiple myeloma (MM) is a hematological malignancy characterized by os-teolytic bone disease which is associated with severe bone pain and pathological bone

fractures. The receptor activator of nuclear factor κB (RANK) and receptor activator of

nuclear factor κB ligand (RANKL) system has an important role in regulation of bone

remodeling process. The aim of this study was to evaluate the expression of the RANK/ RANKL molecules by the myeloma cells derived from patients and myeloma cell line U-266.

Materials and Methods: Myeloma cells derived from 7 myeloma patients and plasma cell leukemia were included into this study to evaluate the expression of the RANK/RANKL molecules by the reverse transcriptions-polymerase chain reaction (RT-PCR) method at the mRNA level. As well as human myeloma cell line U266, U937, RPMI-8866 and Hela were used as control groups.

Results: In this study we show the expression of RANK and its ligand at the mRNA level in U-266 (myeloma cell line) and plasma cells derived from patients by the RT-PCR tech-nique.

Conclusion: Our results demonstrate that expression of RANK and RANKL by plasma cells can contribute to induction of osteoclasts and plasma cell activation which elevates bone resorption in myeloma patients.

Keywords: Multiple Myeloma, Bone Disease, RANKL, RANK

Original Article

(2)

ﻪﻣﺪﻘﻣ

ﺪﻨﺷﺎﺑﻲﻣﺎﻫﻱﺭﺎﻤﻴﺑ ﺯﺍﻲﻌﻴﺳﻭﻒﻴﻃ ﻞﻣﺎﺷﻞﺳﺎﻤﺳﻼﭘ ﺕﻻﻼﺘﺧﺍ Multiple Myeloma;) ﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣ :ﺯﺍﺪﻨﺗﺭﺎﺒﻋ ﺎﻬﻧﺁﺯﺍﻲﺧﺮﺑﻪﻛ

ﻭﻪﻴﻟﻭﺍﺲﻳﺯﻭﺪﻴﻳﻮﻠﻴﻣﺁ،ﺺﺨﺸﻣﺎﻧﺖﻴﻤﻫﺍﺎﺑﻲﺗﺎﭘﺎﻣﺎﮔﻝﺎﻧﻮﻠﻛﻮﻧﻮﻣ،(MM ﻦﻳﺮﺗﻢﻬﻣﻪﻠﻤﺟﺯﺍ .(1) ﻦﻴﻟﻮﺑﻮﻠﮔﻮﻧﻮﻤﻳﺍﻦﻴﮕﻨﺳﻭﻚﺒﺳﻩﺮﻴﺠﻧﺯﻱﺎﻫﻱﺭﺎﻤﻴﺑ

ﺰﻐﻣﺭﺩﻝﺎﻧﻮﻠﻛﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻊﻤﺠﺗﻭﺮﻴﺜﻜﺗ،ﺕﻻﻼﺘﺧﺍﻦﻳﺍﻱﺎﻫﻲﮔﮋﻳﻭ ﻝﺎﻧﻮﻠﻛﻮﻧﻮﻣﻦﻴﻟﻮﺑﻮﻠﮔﻮﻧﻮﻤﻳﺍﺯﺍﻲﺗﻭﺎﻔﺘﻣﻉﺍﻮﻧﺍﻭﺮﻳﺩﺎﻘﻣﺭﻮﻀﺣﻭﻥﺍﻮﺨﺘﺳﺍ

.(3 ،2) ﺪﺷﺎﺑﻲﻣﻥﺍﺭﺎﻤﻴﺑﺭﺍﺭﺩﺍﺎﻳﻭﻡﺮﺳﺭﺩ

ﻥﺎﻃﺮﺳﻦﻴﻣﻭﺩ (MM) ﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣ،ﻞﺳﺎﻤﺳﻼﭘﺕﻻﻼﺘﺧﺍﻥﺎﻴﻣﺭﺩ

ﻪﺑﻁﻮﺑﺮﻣ ﻲﻤﻴﺧﺪﺑﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣ .ﺪﺷﺎﺑﻲﻣﻡﻮﻔﻨﻟ ﺯﺍﺲﭘﻥﻮﺧﻊﻳﺎﺷ

ﻦﻳﺮﺗﻢﻬﻣﺯﺍﻲﺧﺮﺑ .ﺪﺷﺎﺑﻲﻣ (ﺎﻫﻞﺳﺎﻤﺳﻼﭘ) ﻪﺘﻓﺎﻳﺰﻳﺎﻤﺗBﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟ ﻝﺎﻧﻮﻠﻛﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻊﻤﺠﺗﻭﺮﻴﺜﻜﺗ :ﺯﺍﺪﻨﺗﺭﺎﺒﻋﻱﺭﺎﻤﻴﺑﻦﻳﺍﺕﺎﺼﺨﺸﻣ

ﺭﺍﺭﺩﺍﺎﻳﻭﻡﺮﺳﺭﺩﻝﺎﻧﻮﻠﻛﻮﻧﻮﻣﻦﻴﻟﻮﺑﻮﻠﮔﻮﻧﻮﻤﻳﺍﺭﻮﻀﺣ،ﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣﺭﺩ ﻥﺍﺭ،ﻦﮕﻟﻱﺎﻫﻥﺍﻮﺨﺘﺳﺍ،ﻪﻤﺠﻤﺟﺭﺩﻚﻴﺘﻴﻟﻲﻧﺍﻮﺨﺘﺳﺍﺕﺎﻌﻳﺎﺿﺩﺎﺠﻳﺍﻭ ﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣ،ﻲﻧﺎﻣﺭﺩﻦﻳﻮﻧﻱﺎﻫﺖﻓﺮﺸﻴﭘﻪﺑﻲﺑﺎﻳﺖﺳﺩﻑﻼﺧﺮﺑ .ﻩﺮﻴﻏﻭ .ﺩﻮﺷﻲﻣﻪﺘﻓﺮﮔﺮﻈﻧﺭﺩﻥﺎﻣﺭﺩﻞﺑﺎﻗﺮﻴﻏﻱﺭﺎﻤﻴﺑﻚﻳﺕﺭﻮﺻﻪﺑﻥﺎﻨﭽﻤﻫ

ﻲﻨﺳﻦﻴﮕﻧﺎﻴﻣ.ﺪﻧﻮﺷﻲﻣﻼﺘﺒﻣﻱﺭﺎﻤﻴﺑﻦﻳﺍﻪﺑﺮﻔﻧ 15000 ﺩﻭﺪﺣﻝﺎﺳﺮﻫ

ﺮﺘﻤﻛﺺﻴﺨﺸﺗﻥﺎﻣﺯﺭﺩ،ﺪﺷﺎﺑﻲﻣﻲﮕﻟﺎﺳ 60-65 ﻦﻴﺑﺺﻴﺨﺸﺗﻥﺎﻣﺯﺭﺩ

ﺮﻈﻧﻪﺑﺭﻮﻃﻦﻳﺍ .ﺪﻧﺭﺍﺩﻝﺎﺳ 40 ﺯﺍﺮﺘﻤﻛﻦﺳﺎﻣﻮﻠﻳﺎﻣﻪﺑﻥﺎﻳﻼﺘﺒﻣ،ﺪﺻﺭﺩ2 ﺯﺍ

ﺖﻠﻋﻞﻣﺎﻛﺭﻮﻃﻪﺑ .ﺪﺷﺎﺑﻲﻣﻥﺎﻧﺯﺯﺍﺮﺗﻊﻳﺎﺷﻥﺍﺩﺮﻣﺭﺩﺎﻣﻮﻠﻳﺎﻣﻪﻛﺪﺳﺭﻲﻣ

ﻂﻳﺍﺮﺷﻭﻲﻧﻮﻣﺭﻮﻫﺕﺍﺮﺛﺍﻞﻴﻟﺩﻪﺑﺪﻧﺍﻮﺗﻲﻣﺎﻣﺍﺖﺴﻴﻧﺺﺨﺸﻣﺮﻣﺍﻦﻳﺍ ﺩﺭﺩ،ﻲﻧﻮﺧﻢﻛﺮﻴﻈﻧﻲﻤﻳﻼﻋﻱﺍﺭﺍﺩﺎﻣﻮﻠﻳﺎﻣﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑ .ﺪﺷﺎﺑﻱﺭﺎﻛ

ﺖﺳﻼﻛﻮﺌﺘﺳﺍ

ﻱﺎﻫ

ﻝﻮﻠﺳ

ﺖﻴﻟﺎﻌﻓ

ﺭﺩ

ﻲﻳﺎﻣﻮﻠﻳﺎﻣ

ﻱﺎﻫ

ﻝﻮﻠﺳ

ﺶﻘﻧ

،3

،.M.D.D ﻲﻠﻌﺤﺘﻓﺝﺎﺣﺱﺎﺒﻋ، 2

،.Ph.D.Dﻚﭘﻮﭘﺩﺍﺰﻬﺑ، *1

،.Ph.D.Dﻥﻭﺮﺑﺁﺪﻴﻌﺳ، 1

،.M.Sc.Dﻲﻗﺩﺎﺻﻩﺭﺎﻬﺑ 1

،

.

M.Sc.Dﻒﻗﺍﻭﻪﻤﺠﻧ

،1

،

.

M.Sc.Dﻲﻛﺎﺳﻦﻳﺪﻟﺍﻢﺠﻧ

ﻥﺍﺮﻳﺍ،ﻥﺍﺮﻬﺗ،ﻥﻮﺧﻚﻧﺎﺑﻭﻲﺳﺎﻨﺷﻥﻮﺧﻩﻭﺮﮔ،ﻲﻜﺷﺰﭘﻩﺪﻜﺸﻧﺍﺩ،ﺱﺭﺪﻣﺖﻴﺑﺮﺗﻩﺎﮕﺸﻧﺍﺩ .1

ﻥﺍﺮﻳﺍ،ﻥﺍﺮﻬﺗ،ﻲﻜﺷﺰﭘﺍﺮﻴﭘﻩﺪﻜﺸﻧﺍﺩ،ﻝﺎﻤﺷﻥﺍﺮﻬﺗﺪﺣﺍﻭﻲﻣﻼﺳﺍﺩﺍﺯﺁﻩﺎﮕﺸﻧﺍﺩ .2

ﻥﺍﺮﻳﺍ،ﻥﺍﺮﻬﺗ،ﻲﻧﺎﻘﻟﺎﻃﻥﺎﺘﺳﺭﺎﻤﻴﺑ،ﻲﺘﺸﻬﺑﺪﻴﻬﺷﻲﻜﺷﺰﭘﻡﻮﻠﻋﻩﺎﮕﺸﻧﺍﺩ .3

ﻥﻮﺧﻚﻧﺎﺑﻭﻲﺳﺎﻨﺷﻥﻮﺧﻩﻭﺮﮔ،ﻲﻜﺷﺰﭘﻩﺪﻜﺸﻧﺍﺩ،ﺱﺭﺪﻣﺖﻴﺑﺮﺗﻩﺎﮕﺸﻧﺍﺩ،14115-331 :ﻲﺘﺴﭘﻕﻭﺪﻨﺻ،ﻥﺍﺮﻬﺗ،ﻥﺍﺮﻳﺍ :ﻝﻮﺌﺴﻣﻩﺪﻨﺴﻳﻮﻧﺱﺭﺩﺁ *

Email: abroun@modares.ac.ir:ﻚﻴﻧﻭﺮﺘﻜﻟﺍﺖﺴﭘ

89/6/29 :ﻪﻟﺎﻘﻣﺵﺮﻳﺬﭘ،89/3/31 :ﻪﻟﺎﻘﻣﺖﻓﺎﻳﺭﺩ

ﻩﺪﻴﻜﭼ

ﺖﺳﻼﻛﻮﺌﺘﺳﺍﻱﺎﻫﻝﻮﻠﺳﺖﻴﻟﺎﻌﻓﺭﺩﻲﻳﺎﻣﻮﻠﻳﺎﻣﻱﺎﻫﻝﻮﻠﺳﺶﻘﻧﻲﺳﺭﺮﺑ :ﻑﺪﻫ * ﻭﻞﺳﺎﻤﺳﻼﭘ ﻲﻤﺳﻮﻟﻭﺎﻣﻮﻠﻳﺎﻣ ﻪﺑﻼﺘﺒﻣ ﺭﺎﻤﻴﺑ 7 ﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣ ﻭ ﻲﻄﻴﺤﻣﻥﻮﺧ ﻪﻧﻮﻤﻧ ﻪﻌﻟﺎﻄﻣﻦﻳﺍ ﺭﺩ :ﺎﻫﺵﻭﺭ ﻭ ﺩﺍﻮﻣ * ﻭ Receptor Activator of Nuclear Factor κB (RANK) ﻥﺎﻴﺑ ﺮﻈﻧ ﺯﺍ ﻝﺮﺘﻨﻛ ﻪﻧﻮﻤﻧ ﻥﺍﻮﻨﻋ ﻪﺑ ﻲﻟﻮﻠﺳ ﻩﺩﺭ ﻉﻮﻧ 4ﺰﻴﻧ

ﺕﺎﻧﺎﻴﺳﻮﻴﺗﻦﻳﺪﻴﻧﺍﻮﮔﺵﻭﺭﺯﺍﻩﺩﺎﻔﺘﺳﺍﺎﺑﺎﻫﻪﻧﻮﻤﻧRNA.ﺪﺷﻲﺳﺭﺮﺑReceptor Activator of Nuclear Factor κB ligand (RANKL)

ﻥﺎﻴﺑﺖﻴﻌﺿﻭﻲﺑﺎﻳﺯﺭﺍﺖﻬﺟﻲﻔﻴﻛﻝﺮﺘﻨﻛﻡﺎﺠﻧﺍﺯﺍﺲﭘ .ﺪﻳﺩﺮﮔﺝﺍﺮﺨﺘﺳﺍﻥﺍﺭﺎﻤﻴﺑﻪﻧﻮﻤﻧﺯﺍﻩﺪﻣﺁﺖﺳﺩﻪﺑﻱﺍﻪﺘﺴﻫﻚﺗﻱﺎﻫﻝﻮﻠﺳﺯﺍ .ﺪﺷﻩﺩﺎﻔﺘﺳﺍReverse Transcriptions-Polymerase Chain Reaction (RT-PCR)ﺶﻨﻛﺍﻭﺯﺍRANK/RANKL

ﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻭ (ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭ) U-266ﻪﻛﺪﺷﻩﺩﺍﺩﻥﺎﺸﻧ RT-PCRﻚﻴﻨﻜﺗﺯﺍﻩﺩﺎﻔﺘﺳﺍﺎﺑﻪﻌﻟﺎﻄﻣﻦﻳﺍﺭﺩ :ﺎﻫﻪﺘﻓﺎﻳ *

.ﺪﻨﻨﻛﻲﻣﻥﺎﻴﺑ mRNAﺢﻄﺳﺭﺩﺍﺭRANKLﻭRANKﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑﺯﺍﻩﺪﺷﺍﺪﺟ

ﺖﻴﻟﺎﻌﻓﻱﺎﻘﻟﺍﺭﺩﺪﻧﺍﻮﺗﻲﻣﺎﻫﻞﺳﺎﻤﺳﻼﭘﻂﺳﻮﺗ RANKLﻭ RANKﻥﺎﻴﺑﺩﺎﻳﺯﻝﺎﻤﺘﺣﺍﻪﺑﻪﻛﺪﻫﺩﻲﻣﻥﺎﺸﻧﺞﻳﺎﺘﻧ :ﻱﺮﻴﮔﻪﺠﻴﺘﻧ *

.ﺪﺷﺎﺑﻪﺘﺷﺍﺩﻲﻤﻬﻣﺶﻘﻧﺎﻣﻮﻠﻳﺎﻣﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑﺭﺩﻥﺍﻮﺨﺘﺳﺍﺐﻳﺮﺨﺗﺶﻳﺍﺰﻓﺍﻥﺁﺐﻗﺎﻌﺘﻣﻭﺎﻫﻞﺳﺎﻤﺳﻼﭘﻭﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍ

RANK ،RANKL،ﻲﻧﺍﻮﺨﺘﺳﺍﻱﺭﺎﻤﻴﺑ،ﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣ:ﻥﺎﮔژﺍﻭﺪﻴﻠﻛ *

ﻲﺒﺼﻋ ﺕﻻﻼﺘﺧﺍ ،ﻱﺰﻳﺭﻥﻮﺧ ،ﻚﻳژﻮﻟﻮﺗﺎﭘ ﻱﺎﻫﻲﮕﺘﺴﻜﺷ ،ﻥﺍﻮﺨﺘﺳﺍ ﺎﻳﻭﺭﻮﻣﻮﺗﺭﺎﺑﺶﻳﺍﺰﻓﺍﺖﻠﻋﻪﺑﺽﺭﺍﻮﻋﻦﻳﺍ .ﺪﻨﺷﺎﺑﻲﻣﻪﻴﻠﻛﻱﺭﺎﺠﻨﻫﺎﻧﻭ

ﺪﻧﻮﺷﻲﻣﺩﺎﺠﻳﺍﻢﻴﺧﺪﺑﻞﺳﺎﻤﺳﻼﭘﻂﺳﻮﺗﺎﻫﻦﻳﺎﻛﻮﺘﻳﺎﺳﺯﺍﻱﺮﺳﻚﻳﺢﺷﺮﺗ

.(2 ،1)

ﻪﺘﻓﺮﮔﺮﻈﻧﺭﺩﻥﺎﻣﺭﺩﻞﺑﺎﻗﺮﻴﻏﻱﺭﺎﻤﻴﺑﻚﻳﻥﺍﻮﻨﻋﻪﺑﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣ ﺎﻬﻧﺁﻱﺎﻘﺑﻥﺍﺰﻴﻣ،ﺪﻧﻮﺷﻥﺎﻣﺭﺩﺩﺭﺍﺪﻧﺎﺘﺳﺍﺕﺭﻮﺻﻪﺑﻥﺍﺭﺎﻤﻴﺑﺮﮔﺍ .ﺩﻮﺷﻲﻣ

ﺎﻳﻻﺎﺑﺯﻭﺩﺎﺑﻲﻧﺎﻣﺭﺩﻲﻤﻴﺷﺖﺤﺗﻪﻛﻲﺗﺭﻮﺻﺭﺩﻭﻝﺎﺳ 3 ﻦﻴﮕﻧﺎﻴﻣﺭﻮﻃﻪﺑ .(3) ﺪﺷﺎﺑﻲﻣﻝﺎﺳ 5 ،ﺪﻧﺮﻴﮕﺑﺭﺍﺮﻗﺪﻧﻮﻴﭘ

ﻱﺎﻫﺭﻮﺘﻛﺎﻓﺯﺍﻱﺩﺍﺪﻌﺗﻲﻳﺎﻣﻮﻠﻳﺎﻣﻱﺎﻫﻝﻮﻠﺳﻪﻛﺖﺳﺍﻩﺩﺍﺩﻥﺎﺸﻧﺕﺎﻘﻴﻘﺤﺗ

ﺍﺭ(Osteoclast Activating Factors; OAFs)ﺖﺳﻼﻛﻮﺌﺘﺳﺍﻩﺪﻨﻨﻛﻝﺎﻌﻓ

ﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﺖﻴﻟﺎﻌﻓﻭﻱﺮﻴﮔﻞﻜﺷﺶﻳﺍﺰﻓﺍﺚﻋﺎﺑﻖﻳﺮﻃﻦﻳﺍﺯﺍﻭﺪﻨﻨﻛﻲﻣﺢﺷﺮﺗ

3 ﻦﻴﻛﻮﻟﺮﺘﻨﻳﺍ،ﻦﻴﺴﻛﻮﺗﻮﻔﻨﻟﻞﻣﺎﺷﺎﻫﺭﻮﺘﻛﺎﻓﻦﻳﺍﺯﺍﻲﻀﻌﺑ .(5 ،4) ﺪﻧﻮﺷﻲﻣ

،(Interleukin-1; IL-1) 1 ﻦﻴﻛﻮﻟﺮﺘﻨﻳﺍ ،(Interleukin-3; IL-3)

Macrophage (MIP-1α) ،Tumor Necrosis Factor-α (TNF-α)

Transforming Growth (TGF-β)ﻭ Inflammatory Protein-1α

ﻪﻛﺖﺳﺍ ﻩﺩﺍﺩﻥﺎﺸﻧ ﺎﻫﻲﺳﺭﺮﺑ .(1 ﻞﻜﺷ) (7 ،6) ﺪﻨﺷﺎﺑﻲﻣ Factor-β ﺶﻘﻧﻝﺎﻣﻭﺮﺘﺳﺍﻱﺎﻫﻝﻮﻠﺳﻭﻲﻳﺎﻣﻮﻠﻳﺎﻣﻱﺎﻫﻝﻮﻠﺳﻦﻴﺑﻞﺑﺎﻘﺘﻣﻱﺎﻫﺶﻨﻛﺍﻭ ﺭﺩ .ﺪﻧﺭﺍﺩﺎﻣﻮﻠﻳﺎﻣﻪﺑﻥﺎﻳﻼﺘﺒﻣﺭﺩﻲﻧﺍﻮﺨﺘﺳﺍﺕﺎﻌﻳﺎﺿﺩﺎﺠﻳﺍﺭﺩﻲﻤﻬﻣﺭﺎﻴﺴﺑ

ﺶﻘﻧ RANKL/RANKﻢﺘﺴﻴﺳﻪﻛﺖﺳﺍﻩﺪﺷﺵﺭﺍﺰﮔﺪﻳﺪﺟﺕﺎﻌﻟﺎﻄﻣ

ﻲﻓﺮﻃﺯﺍ .(9 ،8 ،4) ﺩﺭﺍﺩﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﺖﻴﻟﺎﻌﻓﻭﻱﺮﻴﮔﻞﻜﺷﺭﺩﻲﻤﻬﻣ

RANK/RANKLﻢﺘﺴﻴﺳﻢﻴﻈﻨﺗﺭﺩﻝﻼﺘﺧﺍﻪﻛﺪﻨﻨﻛﻲﻣﺭﺎﻬﻇﺍﻦﻴﻘﻘﺤﻣ

ﺎﻣﻮﻠﻳﺎﻣﻪﺑﻥﺎﻳﻼﺘﺒﻣﻲﻧﺍﻮﺨﺘﺳﺍﻱﺭﺎﻤﻴﺑﺰﻧژﻮﺗﺎﭘﺭﺩﻲﺘﻴﻤﻫﺍﺎﺑﺶﻘﻧﺪﻧﺍﻮﺗﻲﻣ

(3)

ﺩﺎﺠﻳﺍﺭﺩﻪﻛﻲﻳﺎﻫﺭﻮﺘﻛﺎﻓﺯﺍﻲﺧﺮﺑﻪﺑﻁﻮﺑﺮﻣﻚﻴﺗﺎﻤﺷﺮﻳﻮﺼﺗ :1 ﻞﻜﺷ .ﺪﻧﺭﺍﺩﺶﻘﻧﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣﺭﺩﻲﻧﺍﻮﺨﺘﺳﺍﻱﺮﻴﮔﺭﺩ

ﺯﺍ ﻱﻮﻀﻋ ﻭ ﺖﺳﺍ ﻚﻳﺮﻤﻳﺍﺮﺗﻮﻤﻫ ﻦﻴﺌﺗﻭﺮﭘ ﻚﻳ RANK ،ﺖﺳﻼﻛﻮﺌﺘﺳﺍﺯﺎﺳﺶﻴﭘ .ﺪﺷﺎﺑﻲﻣ TNF-Receptor Super Family ﻥﺎﻴﺑﺍﺭﻦﻴﺌﺗﻭﺮﭘﻦﻳﺍﻲﻧﺎﺘﺴﭘﺩﺪﻏﻭﻚﻴﺗﺭﺪﻧﺩﻝﻮﻠﺳ،ﻎﻟﺎﺑﺖﺳﻼﻛﻮﺌﺘﺳﺍ ﺪﻨﻧﺎﻣ ﻱﺭﻮﻣﻮﺗﻱﺎﻫﻝﻮﻠﺳﺯﺍﻲﺧﺮﺑﻂﺳﻮﺗ RANKﻲﻓﺮﻃﺯﺍ .ﺪﻨﻨﻛﻲﻣ

ﺎﻫﺭﻮﻣﻮﺗﻦﻳﺍﺯﺎﺘﺳﺎﺘﻣﺭﺩﻭﺩﻮﺷﻲﻣﻥﺎﻴﺑﺰﻴﻧﺕﺎﺘﺳﻭﺮﭘﻥﺎﻃﺮﺳﻭﻪﻨﻴﺳﻥﺎﻃﺮﺳ

.(11 ،10) ﺩﺭﺍﺩﺶﻘﻧﻥﺍﻮﺨﺘﺳﺍﺖﻓﺎﺑﻪﺑ

ﺮﭘﻮﺳﺯﺍﻱﺪﻳﺪﺟﻮﻀﻋﻭﻚﻳﺮﻤﻳﺍﺮﺗﻮﻤﻫﻦﻴﺌﺗﻭﺮﭘ RANKLﻝﻮﻜﻟﻮﻣ .(10-12) ﺪﺷﺎﺑﻲﻣ TNF-Family of Ligandﻲﻠﻴﻣﺎﻓ ﺖﺳﺍﻩﺪﻳﺩﺮﮔﻊﻗﺍﻭ 14q13ﻡﻭﺯﻮﻣﻭﺮﻛﻱﻭﺭﻥﺎﺴﻧﺍﺭﺩ RANKLﻥژ ﻩﺪﺷﻞﻴﻜﺸﺗﻪﻨﻴﻣﺁﺪﻴﺳﺍ 317 ﺯﺍﻥﺁﻦﻴﺌﺗﻭﺮﭘ .ﺪﺷﺎﺑﻲﻣﻥﻭﺰﮔﺍ 5 ﻞﻣﺎﺷﻭ

.ﺪﺷﺎﺑﻲﻣ Alternative Splicingﺕﺭﻮﺻﻪﺑ RANKLﻥژﻥﺎﻴﺑ .ﺖﺳﺍ

ﻱﺎﻫﻙﻼﭘﺱﻮﻤﻴﺗ،ﻥﺍﻮﺨﺘﺳﺍ،ﻲﻄﻴﺤﻣﻱﻭﺎﻔﻨﻟﺩﺪﻏﻂﺳﻮﺗ RANKL ﻥﺍﺰﻴﻣﻪﺑﺪﺒﻛﻭﻪﻳﺭ،ﻲﺘﻜﻠﺳﺍﺕﻼﻀﻋ،ﻪﻴﻠﻛ،ﺖﺳﻮﭘ،ﺐﻠﻗ،ﺰﻐﻣ،ﺮﻳﻲﭘ ،ﻝﺎﻣﻭﺮﺘﺳﺍ،ﺖﺳﻼﺑﻮﺌﺘﺳﺍ،ﻩﺪﺷﻝﺎﻌﻓTﻭ Bﻱﺎﻫﻝﻮﻠﺳ .ﺩﻮﺷﻲﻣﻥﺎﻴﺑﺩﺎﻳﺯ

ﺢﺷﺮﺗﺍﺭﻦﻴﺌﺗﻭﺮﭘﻦﻳﺍﺖﻴﺳﻭﺭﺪﻨﻛﻭﻝﺎﻴﻠﺗﻭﺪﻧﺍ،ﺖﺳﻼﺑﻭﺮﺒﻴﻓ،ﻝﺎﻳﻭﻮﻨﻴﺳ ﺲﻳﺰﻧژﻮﺘﺳﻼﻛﻮﺌﺘﺳﺍﺭﺩﻱﺩﺪﻌﺘﻣﻱﺎﻫﺶﻘﻧﻱﺍﺭﺍﺩﻦﻴﺌﺗﻭﺮﭘﻦﻳﺍ؛ﺪﻨﻨﻛﻲﻣ

:ﺖﺳﺍﺮﻳﺯﺡﺮﺷﻪﺑﺪﺷﺎﺑﻲﻣ

ﻞﻴﻜﺸﺗﺮﮕﻳﺪﻜﻳﻪﺑﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﻱﺎﻫﺯﺎﺳﺶﻴﭘﻥژﻮﻴﻓﻭﻝﺎﺼﺗﺍ ﺖﺳﻼﻛﻮﺌﺘﺳﺍﻪﺑﺖﺳﻼﻛﻮﺌﺘﺳﺍﻱﺎﻫﺯﺎﺳﺶﻴﭘﺰﻳﺎﻤﺗ،ﻱﺍﻪﺘﺴﻫﺪﻨﭼﻱﺎﻫﻝﻮﻠﺳ ﻥﺩﺮﻛﻝﺎﻌﻓ،ﻥﺍﻮﺨﺘﺳﺍﺡﻮﻄﺳﻪﺑﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﻥﺪﻴﺒﺴﭼﻭﻝﺎﺼﺗﺍ،ﻎﻟﺎﺑ ﺲﻳﺯﻮﺘﭘﻮﭘﺁﺯﺍﻱﺮﻴﮔﻮﻠﺟﺏﺬﺟﺯﺎﺑﺭﺩﺖﻛﺮﺷﺭﻮﻈﻨﻣﻪﺑﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍ

.(12) ﺪﺷﺎﺑﻲﻣﺎﻫﻝﻮﻠﺳﻦﻳﺍﻱﺎﻘﺑﻆﻔﺣﻭﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍ

ﺶﻳﺍﺰﻓﺍﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﻱﺎﻘﺑﻭﺮﻴﺜﻜﺗ،RANKﻥﺪﺷﻝﺎﻌﻓﻝﺎﺒﻧﺩﻪﺑ ﺎﻬﻧﺁﻥﺪﺷﻝﺎﻌﻓﻭﺮﮕﻳﺪﻜﻳﻪﺑﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﻝﺎﺼﺗﺍﻲﻓﺮﻃﺯﺍ،ﺪﺑﺎﻳﻲﻣ ﻦﻳﺍﺖﻴﻟﺎﻌﻓﺶﻳﺍﺰﻓﺍﻭﺩﺍﺪﻌﺗﺶﻳﺍﺰﻓﺍﻪﺑﺮﺠﻨﻣﺖﻳﺎﻬﻧﺭﺩﻪﻛﺪﻫﺩﻲﻣﻱﻭﺭ ﻖﻳﺮﻃﺯﺍﻝﻮﻜﻟﻮﻣﻦﻳﺍ RANKﻥﺪﺷﻝﺎﻌﻓﻝﺎﺒﻧﺩﻪﺑ .(12) ﺩﻮﺷﻲﻣﺎﻫﻝﻮﻠﺳ

Extracellular ﻦﻣﻭﺩ ﻪﺑ Cysteine-Rich TNFR like ﻱﺎﻫﻦﻣﻭﺩ

ﺎﻫﺶﻨﻛﺍﻭﻦﻳﺍ .ﺩﻮﺷﻲﻣﻞﺼﺘﻣ RANKLﻝﻮﻜﻟﻮﻣ Receptor Binding ﻲﺗﻭﺎﻔﺘﻣﻉﺍﻮﻧﺍﻥﺪﺷﻝﺎﻌﻓﻥﺁﺐﻗﺎﻌﺘﻣﻭ RANKﻥﻮﻴﺳﺍﺰﻳﺮﻣﻮﮕﻴﻟﺍﻪﺑﺮﺠﻨﻣ ﻱﺎﻫﻥژ ﺯﺍﻱﺭﺎﻴﺴﺑﺖﻳﺎﻬﻧ ﺭﺩﻭ ﺩﺩﺮﮔﻲﻣﻝﺎﻨﮕﻴﺳﻝﺎﻘﺘﻧﺍﻱﺎﻫﺮﻴﺴﻣﺯﺍ ،ﻦﻴﻧﻮﺗﻲﺴﻠﻛ ﻩﺪﻧﺮﻴﮔ ،K ﻦﻴﺴﭙﺗﺎﻛ ﺪﻨﻧﺎﻣ ﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍ ﻲﺻﺎﺼﺘﺧﺍ .(2 ﻞﻜﺷ) (13 ،12) ﺪﻧﻮﺷﻲﻣﻥﺎﻴﺑ TRAPﻭβ3 ،OSCARﻦﻳﺮﮕﺘﻨﻳﺍ ﻢﻴﻈﻨﺗﺭﺩﺕﻭﺎﻔﺘﻣﻝﺎﻨﮕﻴﺳﻝﺎﻘﺘﻧﺍﻱﺎﻫﺮﻴﺴﻣﻖﻳﺮﻃﺯﺍ RANK signaling

:ﺯﺍﺪﻨﺘﺴﻫﺕﺭﺎﺒﻋﺎﻬﻧﺁﺯﺍﻲﺧﺮﺑﻪﻛﺩﺭﺍﺩﺶﻘﻧﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﺖﻴﻟﺎﻌﻓ

NF-κBﻝﺎﻨﮕﻴﺳﻝﺎﻘﺘﻧﺍﺮﻴﺴﻣ .1 JNKﻝﺎﻨﮕﻴﺳﻝﺎﻘﺘﻧﺍﺮﻴﺴﻣ .2

AKT-PTKﻝﺎﻨﮕﻴﺳﻝﺎﻘﺘﻧﺍﺮﻴﺴﻣ .3

ﻥﺍﻮﻨﻋﻪﺑTRAF 6 ﻝﻮﻜﻟﻮﻣ RANKﻪﺑ RANKLﻝﺎﺼﺗﺍﻝﺎﺒﻧﺩﻪﺑ

.ﺩﻮﺷﻲﻣﻞﺼﺘﻣ RANKﻲﻟﻮﻠﺳﻞﺧﺍﺩﻦﻣﻭﺩﺯﺍﻲﺻﺎﺧﻲﺣﺍﻮﻧﻪﺑﺭﻮﺘﭘﺍﺩﺁ

ﻚﻴﺗﺎﻤﻳﺰﻧﺁﺖﻴﻟﺎﻌﻓﺪﻗﺎﻓ RANKﻝﻮﻜﻟﻮﻣﻲﻟﻮﻠﺳﻞﺧﺍﺩﻦﻣﻭﺩﻊﻗﺍﻭﺭﺩ

-TNF Receptor Aso) TRAF6ﺯﺍﻝﺎﻨﮕﻴﺳﻝﺎﻘﺘﻧﺍﻪﻣﺍﺩﺍﺖﻬﺟﻪﻛﻩﺩﻮﺑ

ﻱﺮﻴﮔﻞﻜﺷﺭﺩ RANKLﻢﺘﺴﻴﺳﺶﻘﻧﻪﺑﻚﻤﻛ (siated Factor-6

ﻢﻴﻈﻨﺗ ،ﺵﺭﺍﺰﮔ ﻖﺒﻃ .ﺪﺷﻩﺭﺎﺷﺍ ﺮﺼﺘﺨﻣﺭﻮﻃ ﻪﺑ ﻝﺎﻣﺮﻧ ﺖﺳﻼﻛﻮﺌﺘﺳﺍ

ﻥﺍﻮﺨﺘﺳﺍﻥﺪﺷﺰﻴﻟﻪﻠﻤﺟﺯﺍﻲﺗﻻﻼﺘﺧﺍﺚﻋﺎﺑﺪﻧﺍﻮﺗﻲﻣﻢﺘﺴﻴﺳﻦﻳﺍﻲﻌﻴﺒﻃﺮﻴﻏ

.(14 ،9 ،8) ﺩﺮﻛﻩﺭﺎﺷﺍﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣﺎﻫﻱﺭﺎﻤﻴﺑﻪﺑﻥﺍﻮﺗﻲﻣﻪﻛﺪﺷﺎﺑ

ﻝﻮﻠﺳﺭﺩRANKﻝﺎﻨﮕﻴﺳﻝﺎﻘﺘﻧﺍﺮﻴﺴﻣﻪﺑﻁﻮﺑﺮﻣﻚﻴﺗﺎﻤﺷﺮﻳﻮﺼﺗ :2 ﻞﻜﺷ

.http://www.cellsignal.comﺖﺳﻼﻛﻮﺌﺘﺳﺍ

ﻂﻴﺤﻣﺰﻳﺭﺭﺩﻲﻳﺎﻣﻮﻠﻳﺎﻣﻱﺎﻫﻝﻮﻠﺳﺭﻮﻀﺣﻪﻛﺖﺳﺍﻦﻳﺍﺮﺑﺽﺮﻓ

RANKL ،RANK ﻥﺎﻴﺑﻥﺍﺰﻴﻣﺭﺩﺮﻴﻴﻐﺗﺚﻋﺎﺑﻥﺍﺭﺎﻤﻴﺑﻦﻳﺍﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣ

ﻩﺪﺷﺎﻫﻝﻮﻜﻟﻮﻣﻦﻳﺍﻥﺎﻴﺑﺭﺩﻥﺯﺍﻮﺗﻡﺪﻋﺚﻋﺎﺑﺖﻳﺎﻬﻧﺭﺩﻪﻛﺩﻮﺷ OPGﻭ ﻱﺮﻴﮔﻞﻜﺷﺶﻳﺍﺰﻓﺍﺚﻋﺎﺑﻭﻪﺘﻓﺎﻳﺶﻳﺍﺰﻓﺍ RANKLﻥﺎﻴﺑﻪﺠﻴﺘﻧﺭﺩ .ﺖﺳﺍ

ﺐﻳﺮﺨﺗﻥﺎﻤﻫﺎﻳﻥﺍﻮﺨﺘﺳﺍﺏﺬﺟﺶﻳﺍﺰﻓﺍﻥﺁﺐﻗﺎﻌﺘﻣﻭﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍ

.(15) ﺩﺩﺮﮔﻲﻣﻥﺍﻮﺨﺘﺳﺍ

ﻪﺑ ﻭﺎﻫﻝﻮﻜﻟﻮﻣﻦﻳﺍﻥﺎﻴﺑﺭﺩﻥﺯﺍﻮﺗﻡﺪﻋ ﻪﻛﺩﻮﺷﻲﻣﻩﺩﺍﺩﻝﺎﻤﺘﺣﺍ ﻩﺭﺎﺷﺍﺎﻬﻧﺁﻪﺑﻞﻳﺫﺭﺩﻪﻛﻲﻳﺎﻫﺮﻴﺴﻣﻦﻳﺍﻖﻳﺮﻃﺯﺍ RANKLﺹﻮﺼﺧ

:ﺩﻮﺷﺩﺎﺠﻳﺍﺖﺳﺍﻩﺪﺷ

ﺶﻳﺍﺰﻓﺍﺚﻋﺎﺑﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣﺭﺩﺩﻮﺟﻮﻣﻲﻳﺎﻣﻮﻠﻳﺎﻣﻱﺎﻫﻝﻮﻠﺳﺖﺳﺍﻦﻜﻤﻣ .1

ﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣﻂﻴﺤﻣﺰﻳﺭﺭﺩﺩﻮﺟﻮﻣﻱﺎﻫﻝﻮﻠﺳﺯﺍﻲﺧﺮﺑﻂﺳﻮﺗ RANKLﻥﺎﻴﺑ ﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﺖﻴﻟﺎﻌﻓﻭﻱﺮﻴﮔﻞﻜﺷﺶﻳﺍﺰﻓﺍﺚﻋﺎﺑﻢﻴﻘﺘﺴﻣﺮﻴﻏﺕﺭﻮﺻﻪﺑﻭﻩﺪﺷ

.(16 ،15) ﺩﻮﺷﻥﺍﻮﺨﺘﺳﺍﺐﻳﺮﺨﺗﺎﻳﺏﺬﺟﺶﻳﺍﺰﻓﺍﻥﺁﻝﺎﺒﻧﺩﻪﺑﻭ

ﻪﺑ،ﺩﻮﺧ،ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻱﺎﻫﻝﻮﻠﺳﻪﻛﺩﺭﺍﺩﺩﻮﺟﻭﻱﺮﮕﻳﺩﻝﺎﻤﺘﺣﺍ .2

ﻱﺮﻴﮔﻞﻜﺷﺚﻋﺎﺑﻖﻳﺮﻃﻦﻳﺍﺯﺍﻭﺪﻨﻨﻛﻥﺎﻴﺑﺍﺭ RANKLﻢﻴﻘﺘﺴﻣﺕﺭﻮﺻ

.(17 ،15) ﺪﻧﻮﺷﻥﺍﻮﺨﺘﺳﺍﺏﺬﺟﻭﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍ

ﻖﻳﺮﻃﺯﺍﺪﻨﻧﺍﻮﺗﻲﻣﻲﻳﺎﻣﻮﻠﻳﺎﻣﻱﺎﻫﻝﻮﻠﺳﻪﻛﺖﺳﺍﻦﻳﺍﺮﺑﻡﻮﺳﻪﻳﺮﻈﻧ

RANKLﻱﺍﺮﺑ Decoy Receptorﻥﺍﻮﻨﻋﻪﺑﻪﻛ) OPGﺪﻴﻟﻮﺗﺭﺎﻬﻣ

ﻝﺎﺼﺗﺍﻱﺎﺟﻪﺑ RANKLﺕﺭﻮﺻﻦﻳﺍﺭﺩ،ﺪﻨﻨﻛﺎﻔﻳﺍﺍﺭﺩﻮﺧﺶﻘﻧ (ﺪﺷﺎﺑﻲﻣ

ﺶﻳﺍﺰﻓﺍﺚﻋﺎﺑﻖﻳﺮﻃﻦﻳﺍﺯﺍﻭﺪﺑﺎﻳﻲﻣﻝﺎﺼﺗﺍ RANKﻝﻮﻜﻟﻮﻣﻪﺑ OPGﻪﺑ .(18-21) ﺩﻮﺷﻲﻣﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﻱﺮﻴﮔﻞﻜﺷﺶﻳﺍﺰﻓﺍﻭﺖﻴﻟﺎﻌﻓ

(4)

ﺎﻫ

ﺵﻭﺭ

ﻭ

ﺩﺍﻮﻣ

ﺖﻴﺑﺮﺗﻩﺎﮕﺸﻧﺍﺩﻲﻜﺷﺰﭘﻕﻼﺧﺍﻪﺘﻴﻤﻛﺯﻮﺠﻣﺱﺎﺳﺍﺮﺑﺮﺿﺎﺣﻪﻌﻟﺎﻄﻣ ﻪﻣﺎﻧﺖﻳﺎﺿﺭﻪﺑﻁﻮﺑﺮﻣﻡﺮﻓﻭﺪﺷﻡﺎﺠﻧﺍﻲﻜﺷﺰﭘﻡﻮﻠﻋﻩﺪﻜﺸﻧﺍﺩ،ﺱﺭﺪﻣ

.ﺪﻳﺩﺮﮔﺬﺧﺍﻥﺍﺭﺎﻤﻴﺑﻲﻣﺎﻤﺗﺯﺍ

ﻭ ﺎﻣﻮﻠﻳﺎﻣ ﻞﭙﻴﺘﻟﺎﻣﻪﺑ ﻙﻮﻜﺸﻣﻥﺍﺭﺎﻤﻴﺑ ﻪﺑ ﻁﻮﺑﺮﻣ ﺎﻫﻪﻧﻮﻤﻧ ﻲﻣﺎﻤﺗ ﻱﺎﻫﻝﻮﻠﺳﺩﻮﺟﻭﺮﻈﻧﺯﺍﺪﻴﻳﺎﺗﺖﻬﺟﻦﻳﺍﺮﺑﺎﻨﺑ،ﺪﻧﺩﻮﺑﻞﺳﺎﻤﺳﻼﭘﻲﻤﺳﻮﻟ ﻱژﻮﻟﻮﺗﺎﭘﻱﺎﻫﺵﺭﺍﺰﮔ،ﻱﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓﺰﻴﻟﺎﻧﺁﻁﻮﺑﺮﻣﻪﺑﺞﻳﺎﺘﻧﻲﻳﺎﻣﻮﻠﻳﺎﻣ ﻲﻣﺎﻤﺗﻩﺮﻴﭙﺳﺁﺎﻳﻭﻲﻄﻴﺤﻣﻥﻮﺧﻡﻻﻲﺳﺭﺮﺑﻭﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣﻭﻲﺴﭘﻮﻴﺑ ﻥﺍﺭﺎﻤﻴﺑﻦﻳﺍﻲﻜﺷﺰﭘ ﻱﺎﻫﻩﺪﻧﻭﺮﭘ ﻪﺑ ﻁﻮﺑﺮﻣﺵﺭﺍﺰﮔ ﻩﺍﺮﻤﻫﻪﺑﻥﺍﺭﺎﻤﻴﺑ

.ﺪﻧﺪﺷﻲﺳﺭﺮﺑ

ﻥﺍﺭﺎﻤﻴﺑﻲﻄﻴﺤﻣﻥﻮﺧﻭﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣﻱﺎﻫﻪﻧﻮﻤﻧﺯﺍ RNAﻱﺯﺎﺳﺍﺪﺟ ﺵﻭﺭﺯﺍﻩﺩﺎﻔﺘﺳﺍﺎﺑHelaﻭ U-266 ،RPMI ،U-937ﻲﻟﻮﻠﺳﻱﺎﻫﻩﺩﺭﻭ ﺖﻴﻔﻴﻛﺯﺍﻥﺎﻨﻴﻤﻃﺍﻱﺍﺮﺑ .ﺖﻓﺮﮔﺕﺭﻮﺻ Guanidine thiocynate ﻭRNAﺖﻈﻠﻏﻦﻴﻴﻌﺗﻞﻣﺎﺷﻲﻔﻴﻛﻝﺮﺘﻨﻛﻞﺣﺍﺮﻣﻩﺪﺷﺝﺍﺮﺨﺘﺳﺍRNA ﺰﺘﻨﺳ .ﺪﺷﻡﺎﺠﻧﺍ Eppendorfٍﺮﺘﻣﻮﺘﻓﻮﻴﺑﺎﺑ (OD260/280)ﻥﺁﺹﻮﻠﺧ ﺯﺍﻥﺎﻨﻴﻤﻃﺍﻱﺍﺮﺑ .ﺖﻓﺮﮔﺕﺭﻮﺻ M-MULVﻢﻳﺰﻧﺁﺯﺍﻩﺩﺎﻔﺘﺳﺍﺎﺑcDNA ﻲﻳﺎﺳﺎﻨﺷﺭﻮﻈﻨﻣﻪﺑﺯﺍﺮﻤﻴﻠﭘﻩﺮﻴﺠﻧﺯﺶﻨﻛﺍﻭ،ﻩﺪﺷﻪﺘﺧﺎﺳ cDNAﺖﻴﻔﻴﻛ ﻡﺎﺠﻧﺍ (House Keeping Gene)ﺩﺭﺍﺩﻲﮕﺸﻴﻤﻫﻥﺎﻴﺑﻪﻛﻥژﻚﻳ ﻭﻥژﻦﻳﺍﻥﺎﻴﺑﻲﺑﺎﻳﺯﺭﺍﺖﻬﺟβ2μ2ﻥژﻱﺎﻫﺮﻤﻳﺍﺮﭘﺭﻮﻈﻨﻣﻦﻳﺍﻱﺍﺮﺑ .ﺪﺷ

.ﺪﻳﺩﺮﮔﻩﺩﺎﻔﺘﺳﺍcDNAﺖﺧﺎﺳﻝﺮﺘﻨﻛ

RANKﻭ RANKLﻱﺎﻫﻥژﻪﺑﻁﻮﺑﺮﻣ mRNAﻥﺎﻴﺑﻲﺳﺭﺮﺑﺖﻬﺟ

ﻱﺎﻫﺮﻤﻳﺍﺮﭘ،ﺮﻈﻧﺩﺭﻮﻣﻲﻟﻮﻠﺳﻱﺎﻫﻩﺩﺭﻭﻥﺍﺭﺎﻤﻴﺑﻲﻳﺎﻣﻮﻠﻳﺎﻣﻱﺎﻫﻝﻮﻠﺳﺭﺩ ﺎﺑﺯﺎﻴﻧﺩﺭﻮﻣﻱﺎﻫﺮﻤﻳﺍﺮﭘﻲﺣﺍﺮﻃ؛ﺪﻧﺪﺷﻲﺣﺍﺮﻃﻥژﻭﺩﻦﻳﺍﻪﺑ ﻁﻮﺑﺮﻣ ﺪﺷﻡﺎﺠﻧﺍ GENERUNNER ﻭ OLIGO ﻱﺎﻫﺭﺍﺰﻓﺍﻡﺮﻧ ﺯﺍ ﻩﺩﺎﻔﺘﺳﺍ .(2 ﻭ 1 ﻝﻭﺪﺟ) ﺪﻧﺪﺷﺪﻴﻳﺎﺗ،NCBI Blast

ﻝژﺮﺑﻩﻭﻼﻋ PCRﻝﻮﺼﺤﻣﻩﺪﻫﺎﺸﻣﻭﻲﺳﺭﺮﺑﺖﻬﺟﻪﻌﻟﺎﻄﻣﻦﻳﺍﺭﺩ

.ﺪﺷﻩﺩﺎﻔﺘﺳﺍﺰﻴﻧﺪﺻﺭﺩ 1/5 ﺯﺭﺎﮔﺁﻝژﺯﺍﺪﻴﻣﺁﻞﻳﺮﻛﺍﻲﻠﭘ

ﺎﻫ

ﻪﺘﻓﺎﻳ

ﻥﺎﺸﻧ ﻢﻴﺘﺴﻧﺍﻮﺗ RT-PCR ﻚﻴﻨﻜﺗ ﺯﺍﻩﺩﺎﻔﺘﺳﺍ ﺎﺑ ﻪﻌﻟﺎﻄﻣ ﻦﻳﺍﺭﺩ ﺯﺍﻩﺪﺷﺍﺪﺟﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻭ (ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭ) U-266ﻪﻛﻢﻴﻫﺪﺑ

ﻥﺎﻴﺑ mRNAﺢﻄﺳﺭﺩﺍﺭ RANKLﻭ RANK،ﺎﻣﻮﻠﻳﺎﻣﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑ

.(4 ﻭ 3 ﻝﻭﺪﺟ) ﺪﻨﻨﻛﻲﻣ

ﻥﺍﺭﺎﻤﻴﺑﻪﺑﻁﻮﺑﺮﻣRT-PCRﻲﺳﺭﺮﺑﺞﻳﺎﺘﻧ :3 ﻝﻭﺪﺟ

ﻥﺍﺭﺎﻤﻴﺑ P7 P6 P5 P4 P3 P2 P1 + + + + + + + RANKL + + + + + + + RANK

ﻲﻟﻮﻠﺳﻱﺎﻫﻩﺩﺭﻪﺑﻁﻮﺑﺮﻣRT-PCRﻲﺳﺭﺮﺑﺞﻳﺎﺘﻧ :4 ﻝﻭﺪﺟ

ﻲﻟﻮﻠﺳﻱﺎﻫﻩﺩﺭ

HELA RPMI-8866 U-937 U-266 + + + + RANKL -+ + RANK

ﺚﺤﺑ

.(2 ،1) ﺪﺷﺎﺑﻲﻣﺎﻫﻞﺳﺎﻤﺳﻼﭘﻪﺑ ﻁﻮﺑﺮﻣ ﻲﻤﻴﺧﺪﺑ ﺎﻣﻮﻠﻳﺎﻣ ﻞﭙﻴﺘﻟﺎﻣ

ﻦﻳﺍﻱﺎﻫﻲﮔﮋﻳﻭ ﻦﻳﺮﺗﻢﻬﻣﺯﺍﻲﻜﻳ ﻲﻧﺍﻮﺨﺘﺳﺍ ﻩﺪﻧﻭﺭﺶﻴﭘ ﻱﺎﻫﺐﻳﺮﺨﺗ

.ﺖﺳﺍﻱﺭﺎﻤﻴﺑ

ﺖﺳﻼﻛﻮﺌﺘﺳﺍ ﻩﺪﻨﻨﻛ ﻝﺎﻌﻓ ﻱﺎﻫﺭﻮﺘﻛﺎﻓ ﻂﺳﻮﺗ ﻲﻧﺍﻮﺨﺘﺳﺍ ﺐﻳﺮﺨﺗ

.(3) ﺩﻮﺷﻲﻣﺩﺎﺠﻳﺍ (OAF) ﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘ ﻂﺳﻮﺗ ﻲﻌﺿﻮﻣ ﺕﺭﻮﺻ ﻪﺑ ﺎﻳ ﺎﻫﺭﻮﺘﻛﺎﻓ ﻦﻳﺍ ﺪﻧﻮﺷﻲﻣﺪﻴﻟﻮﺗﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣﻝﺎﻣﻭﺮﺘﺳﺍﻱﺎﻫﻝﻮﻠﺳﻂﺳﻮﺗﺎﻳﻭﻝﺎﻧﻮﻠﻛﻮﻧﻮﻣ ﺖﻴﻟﺎﻌﻓﺶﻳﺍﺰﻓﺍﺖﻳﺎﻬﻧﺭﺩﻭﺎﻘﺑ،ﻱﺮﻴﮔﻞﻜﺷ،ﺰﻳﺎﻤﺗﻚﻳﺮﺤﺗﺚﻋﺎﺑﻪﻛ ﻲﺷﺎﻧﺽﺭﺍﻮﻋﻭﻥﺍﻮﺨﺘﺳﺍﺐﻳﺮﺨﺗﺶﻳﺍﺰﻓﺍﻥﺁﺐﻗﺎﻌﺘﻣﻭﺎﻫﺖﺳﻼﻛﻮﺘﺳﺍ ،IL-6 :ﺯﺍﺪﻨﺘﺴﻫﺕﺭﺎﺒﻋ OAFsﻦﻳﺮﺗﻢﻬﻣﺯﺍﻱﺩﺍﺪﻌﺗ .ﺪﻧﻮﺷﻲﻣﻥﺁﺯﺍ

ﺎﻫﺭﻮﺘﻛﺎﻓﻦﻳﺍﺯﺍﻡﺍﺪﻛﭻﻴﻫﻥﺎﻴﺑﻪﻛﺖﺳﺍﻩﺪﺷﺵﺭﺍﺰﮔMIP-1α،IL-1β ﻥﺎﻳﻼﺘﺒﻣﺭﺩﻲﻧﺍﻮﺨﺘﺳﺍﻚﻴﺘﻴﻟﺕﺎﻌﻳﺎﺿﺩﺎﺠﻳﺍﺚﻋﺎﺑﻪﻛﺖﺴﻴﻧﻱﺪﺣﺭﺩ ﺭﺩﻱﺮﮕﻳﺩﻞﻣﺍﻮﻋﺭﻮﻀﺣﻪﻛﺖﻓﺮﮔﻪﺠﻴﺘﻧﻥﺍﻮﺗﻲﻣﺲﭘ .ﺩﻮﺷﺎﻣﻮﻠﻳﺎﻣﻪﺑ .ﺖﺳﺍﺮﺛﻮﻣﺭﻮﻛﺬﻣﺕﺎﻌﻳﺎﺿﺩﺎﺠﻳﺍ

ﺎﻫﺮﻤﻳﺍﺮﭘﺕﺎﺼﺨﺸﻣ :1 ﻝﻭﺪﺟ

Product Size (bp) Cycle No.

Annealing tempreature t (˚C) TM

Sequence (5́ →3́) Primer

194 35

ﺩﺍﺮﮔﻲﺘﻧﺎﺳﻪﺟﺭﺩ 60 59

S:GGGAGCATGTGAAGGTGTCT RANK

194 35

A:GCATCTGTCTGAAGCTGTCT

143 35

S:CCAAGATCTCCAACATGACT RANKL

143 35

A:TACACCATTAGTTGAAGATACT

mRNAﻥﺎﻴﺑﻲﺳﺭﺮﺑﺭﻮﻈﻨﻣﻪﺑ RT-PCRﺶﻨﻛﺍﻭﻪﻣﺎﻧﺮﺑ :2 ﻝﻭﺪﺟ RANKLﻭ RANKﻪﺑﻁﻮﺑﺮﻣ

RANKLﺶﻨﻛﺍﻭ

RANKﺶﻨﻛﺍﻭ

PCRﻞﺣﺍﺮﻣ

ﻪﻘﻴﻗﺩ 2 :ﺩﺍﺮﮔﻲﺘﻧﺎﺳﻪﺟﺭﺩ 94

ﻪﻴﻟﻭﺍﻥﺪﺷﻩﺭﻮﺗﺎﻧﺩ

ﻪﻴﻧﺎﺛ 45 :ﺩﺍﺮﮔﻲﺘﻧﺎﺳﻪﺟﺭﺩ 94

ﻥﺪﺷﻩﺭﻮﺗﺎﻧﺩ

ﺎﻫﺮﻤﻳﺍﺮﭘﻝﺎﺼﺗﺍ

ﻩﺮﻴﺠﻧﺯﺵﺮﺘﺴﮔ

35 35

(5)

ﺖﺒﺴﻧﻭOsteo Protegerion (OPG)/RANK/RANKLﻢﺘﺴﻴﺳ ﻢﻴﻈﻨﺗ ﺭﺩ ﻲﻤﻬﻣﺶﻘﻧ (RANKL: OPG) OPGﻪﺑ RANKL ﻥﺎﻴﺑ ﻭﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﺖﻴﻟﺎﻌﻓﻥﺎﻴﻣﻝﺩﺎﻌﺗﻆﻔﺣﻭﻥﺍﻮﺨﺘﺳﺍﻱﺯﺎﺳﻮﻧﻪﺳﻭﺮﭘ ،ﺪﺷﺎﺑﻲﻣTNFﻲﻠﻴﻣﺎﻓﺮﭘﻮﺳﺯﺍﻱﻮﻀﻋ RANK .(22) ﺩﺭﺍﺩﺎﻫﺖﺳﻼﺑﻮﺌﺘﺳﺍ

ﻥﺍﻮﻨﻋﻪﺑﻭﺩﻮﺷﻲﻣﻥﺎﻴﺑﻎﻟﺎﺑﺖﺳﻼﺑﻮﺌﺘﺳﺍﻭﺖﺳﻼﻛﻮﺌﺘﺳﺍﺯﺎﺳﺶﻴﭘﻂﺳﻮﺗ TNF ﻲﻠﻴﻣﺎﻓ ﺮﭘﻮﺳ ﺯﺍﻱﻮﻀﻋ RANKL .ﺪﺷﺎﺑﻲﻣ RANKL ﻩﺪﻧﺮﻴﮔ .ﺖﺳﺎﺸﻏﻪﺑﻞﺼﺘﻣﻉﻮﻧﻭﻝﻮﻠﺤﻣﻉﻮﻧ :ﻡﺮﻓﻭﺰﻳﺍﻉﻮﻧﻭﺩﻱﺍﺭﺍﺩﻪﻛﺪﺷﺎﺑﻲﻣ

ﻝﺎﻌﻓﺚﻋﺎﺑ (ﻩﺪﻧﺮﻴﮔﻥﺍﻮﻨﻋﻪﺑ) RANKﻪﺑﻝﺎﺼﺗﺍﻖﻳﺮﻃﺯﺍ RANKL ﻥﻭﺭﺩ (ﻩﺮﻴﻏﻭ_NFκ_B_،_JNK) ﻡﺎﻴﭘﻝﺎﻘﺘﻧﺍﻱﺎﻫﺮﻴﺴﻣﺯﺍﻱﺩﺍﺪﻌﺗﻥﺪﺷ

ﻭ ﻍﻮﻠﺑ ، ﺰﻳﺎﻤﺗ ﺚﻋﺎﺑ ﺖﻳﺎﻬﻧ ﺭﺩ ﻭ ﻩﺪﺷ ﺖﺳﻼﻛﻮﺌﺘﺳﺍ ﻱﺎﻫﺯﺎﺳﺶﻴﭘ

.ﺩﻮﺷﻲﻣﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﻱﺮﻴﮔﻞﻜﺷ

ﻩﺪﻧﺮﻴﮔﻥﺍﻮﻨﻋﻪﺑﻭﺪﺷﺎﺑﻲﻣ TNFﻲﻠﻴﻣﺎﻓﺮﭘﻮﺳﺯﺍﻱﻮﻀﻋﺰﻴﻧ OPG

ﻦﻳﺍ ﻪﺑ ﺪﻨﻛﻲﻣ ﻞﻤﻋ RANKL ﻱﺍﺮﺑ (Decoy Receptor) ﻱﺭﺎﻬﻣ

ﺖﻳﺎﻬﻧﺭﺩﻭﻩﺩﺮﻛﺖﻌﻧﺎﻤﻣ RANKﻪﺑ RANKLﻝﺎﺼﺗﺍﺯﺍﻪﻛﺕﺭﻮﺻ .ﺩﻮﺷﻲﻣﺎﻫﺖﺳﻼﻛﻮﺘﺳﺍﺖﻴﻟﺎﻌﻓﻭﻱﺮﻴﮔﻞﻜﺷ،ﺰﻳﺎﻤﺗﺯﺍﺖﻌﻧﺎﻤﻣﺚﻋﺎﺑ

ﻭﻲﻧﺍﻮﺨﺘﺳﺍﻱﺭﺎﻤﻴﺑﺩﺎﺠﻳﺍﻲﻠﺻﺍﻞﻣﺎﻋ RANKLﻪﻛﺖﺳﺍﻦﻳﺍﺮﺑﺽﺮﻓ .ﺪﺷﺎﺑﻲﻣﺎﻣﻮﻠﻳﺎﻣﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑﺭﺩﻥﺁﺯﺍﻲﺷﺎﻧﺽﺭﺍﻮﻋ

ﻥﺎﻴﺑ ﻦﻴﺑ ﻝﺩﺎﻌﺗ ﻡﺪﻋ ﻪﻛ ﺖﺳﺍ ﻩﺩﺍﺩ ﻥﺎﺸﻧ ﻱﺩﺪﻌﺘﻣ ﺕﺎﻌﻟﺎﻄﻣ ﻲﻧﺍﻮﺨﺘﺳﺍﻢﻴﺧﺪﺑﻭﻢﻴﺧﺵﻮﺧﺕﻻﻼﺘﺧﺍﺩﺎﺠﻳﺍﺚﻋﺎﺑ RANKL: OPG ﻭ ﺮﺿﺎﺣ ﻪﻌﻟﺎﻄﻣ ﺯﺍﻞﺻﺎﺣ ﺕﺎﻴﺑﺮﺠﺗ ﻪﺑ ﻪﺟﻮﺗﺎﺑ .ﺪﻧﻮﺷﻲﻣ ﻥﺎﺴﻧﺍ ﺭﺩ :ﺩﺮﻛﻩﺭﺎﺷﺍﻥﺍﻮﺗﻲﻣﺮﻳﺯﻞﻣﺍﻮﻋﻪﺑﻩﺪﺷﺮﺸﺘﻨﻣﺩﺪﻌﺘﻣﻱﺎﻫﺵﺭﺍﺰﮔ

ﻂﺳﻮﺗ mRNAﺢﻄﺳﺭﺩ RANKLﻭ RANKﻥﺎﻴﺑﺮﺿﺎﺣﻪﻌﻟﺎﻄﻣﺭﺩ

-ﻞﺳﺎﻤﺳﻼﭘﻲﻤﺳﻮﻟﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑﻲﻄﻴﺤﻣﻥﻮﺧﺯﺍﻩﺪﺷﺍﺪﺟﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘ ﻲﻟﺎﺣﺭﺩﺪﻨﺘﻓﺮﮔﺭﺍﺮﻗﻲﺑﺎﻳﺯﺭﺍﺩﺭﻮﻣﺎﻣﻮﻠﻳﺎﻣﻪﺑﻥﺎﻳﻼﺘﺒﻣﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣﻩﺮﻴﭙﺳﺁﻭ

ﻂﺳﻮﺗ RANKLﻭRANKﻥﺎﻴﺑﻥﺎﻣﺯﻢﻫﻲﺳﺭﺮﺑﺯﺍﻲﺷﺭﺍﺰﮔﺯﻭﺮﻣﺍﻪﺑﺎﺗﻪﻛ

.ﺖﺳﺍﻩﺪﻳﺩﺮﮕﻧﺮﺸﺘﻨﻣﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭﻭﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳ

،ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻱﺎﻫﻩﺩﺭﻂﺳﻮﺗ RANKLﻥﺎﻴﺑﻲﺑﺎﻳﺯﺭﺍﺩﺭﻮﻣﺭﺩ

-ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭ) 5T2MMﻪﻛﺪﻧﺍﻩﺩﺮﻛﺵﺭﺍﺰﮔﻥﺍﺭﺎﻜﻤﻫﻭﺮﺷﻭﺮﻛ ﺎﺑ ﻥﺍﺭﺎﻜﻤﻫﻭ ﺭﺍﺰﺳﻦﻴﻨﭼﻢﻫ .(22) ﺪﻨﻛﻲﻣﻥﺎﻴﺑﺍﺭ RANKL (ﺵﻮﻣ

ﻩﺩﺎﻔﺘﺳﺍﺎﺑﻥﺍﺭﺎﻜﻤﻫﻭﺭﺪﻴﻫﺰﻴﻧﻭﻲﻤﻴﺷﻮﺘﺴﻴﻫﻮﻧﻮﻤﻳﺍﺵﻭﺭﺯﺍﻩﺩﺎﻔﺘﺳﺍ ﻥﺎﺴﻧﺍﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭﻪﻛﺪﻧﺍﻩﺩﺮﻛﺵﺭﺍﺰﮔﻱﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓﺵﻭﺭﺯﺍ ﻥﺎﺸﻧﻩﺪﻣﺁﺖﺳﺩﻪﺑﺞﻳﺎﺘﻧﺮﺿﺎﺣﻪﻌﻟﺎﻄﻣﺭﺩ .ﺪﻨﻛﻲﻣﻥﺎﻴﺑﺍﺭ RANKL

ﺍﺭ RANKLﻝﻮﻜﻟﻮﻣ U-266ﻲﻧﺎﺴﻧﺍﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭﻪﻛﺪﻫﺩﻲﻣ

.(23) ﺪﻨﻛﻲﻣﻥﺎﻴﺑ mRNAﺢﻄﺳﺭﺩ ﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘ ﻪﻛ ﺪﺷ ﻩﺩﺍﺩ ﻥﺎﺸﻧ ﺮﺿﺎﺣ ﻪﻌﻟﺎﻄﻣ ﺭﺩ ﻦﻴﻨﭼﻢﻫ

-ﻲﻧﺎﺴﻧﺍﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭﻭﺎﻣﻮﻠﻳﺎﻣﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑﻪﻧﻮﻤﻧﺯﺍﻩﺪﺷﺍﺪﺟ ﻲﺗﺭﻮﺻﺭﺩﺪﻨﻨﻛﻲﻣﻥﺎﻴﺑ mRNAﺢﻄﺳﺭﺩﺍﺭ RANKLﻝﻮﻜﻟﻮﻣ،U-266 ﺖﺳﺍﻩﺩﺍﺩﻡﺎﺠﻧﺍ RT-PCRﺵﻭﺭﺯﺍﻩﺩﺎﻔﺘﺳﺍﺎﺑﻲﻧﺎﻴﻟﻮﻴﺟﻪﻛﻲﺳﺭﺮﺑﺭﺩﻪﻛ ﻥﺍﺭﺎﻤﻴﺑﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻂﺳﻮﺗ RANKLﻝﻮﻜﻟﻮﻣﻪﻛﺖﺳﺍﻩﺪﺷﺵﺭﺍﺰﮔ .(24) ﺩﻮﺷﻲﻤﻧﻥﺎﻴﺑﺎﻣﻮﻠﻳﺎﻣﻲﻟﻮﻠﺳﻱﺎﻫﻩﺩﺭﻭﻲﻳﺎﻣﻮﻠﻳﺎﻣ

ﺵﻭﺭ ﺯﺍﻩﺩﺎﻔﺘﺳﺍﺎﺑ ﻥﺍﺭﺎﻜﻤﻫ ﻭ ﺭﺪﻴﺣﻂﺳﻮﺗ ﻪﻛﻱﺍﻪﻌﻟﺎﻄﻣﺭﺩ

-،ﺪﻳﺩﺮﮔﻡﺎﺠﻧﺍ RANKLﻝﻮﻜﻟﻮﻣﻪﻴﻠﻋﻲﺘﻧﺁﺯﺍﻱﺮﻴﮔﺭﺎﻛﻪﺑﻭﻱﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓ

ﺍﺭRANKLﺎﻳﻲﻄﻴﺤﻣﻥﻮﺧﺯﺍﻩﺪﺷﺍﺪﺟﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻪﻛﺪﺷﺵﺭﺍﺰﮔ

.ﺩﺭﺍﺩﺎﻫﻝﻮﻠﺳﻦﻳﺍﺢﻄﺳﺭﺩﻲﻔﻴﻌﺿﻱﺭﺎﻴﺴﺑﻥﺎﻴﺑ RANKLﺎﻳﻭﺪﻨﻨﻛﻲﻤﻧﻥﺎﻴﺑ

ﺭﺩ RANKLﻝﻮﻜﻟﻮﻣﻪﻛﻢﻴﻫﺩﻥﺎﺸﻧﻢﻴﺘﺴﻧﺍﻮﺗﻪﻌﻟﺎﻄﻣﻦﻳﺍﺭﺩﻪﻛﻲﻟﺎﺣﺭﺩ

ﻥﻮﺧﺯﺍﻩﺪﺷﺍﺪﺟﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻂﺳﻮﺗﺺﺨﺸﻣﺭﻮﻃﻪﺑﻭ mRNAﺢﻄﺳ ﺍﺪﺟﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻂﺳﻮﺗﺰﻴﻧﻭﻞﺳﺎﻤﺳﻼﭘﻲﻤﺳﻮﻟﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑﻲﻄﻴﺤﻣ

.(25) ﺩﻮﺷﻲﻣﻥﺎﻴﺑﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣﻪﺑﻥﺎﻳﻼﺘﺒﻣﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣﻩﺮﻴﭙﺳﺁﺯﺍﻩﺪﺷ

ﻲﺳﺭﺮﺑﺮﺑﻲﻨﺒﻣﻲﺷﺭﺍﺰﮔﺯﻭﺮﻣﺍﻪﺑﺎﺗﺪﻳﺩﺮﮔﺮﻛﺫﻪﻛﺭﻮﻃﻥﺎﻤﻫ

-ﻩﺪﺸﻧ ﺮﺸﺘﻨﻣ ﻲﻳﺎﻣﻮﻠﻳﺎﻣ ﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘ ﻂﺳﻮﺗ RANK ﻝﻮﻜﻟﻮﻣ ﻥﺎﻴﺑ ﻢﻴﻫﺩﻥﺎﺸﻧﻢﻴﺘﺴﻧﺍﻮﺗ RT-PCRﺵﻭﺭﺯﺍﻩﺩﺎﻔﺘﺳﺍﺎﺑﻪﻌﻟﺎﻄﻣﻦﻳﺍﺭﺩ .ﺖﺳﺍ

ﻲﻤﺳﻮﻟﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑﻲﻄﻴﺤﻣﻥﻮﺧﺯﺍﻩﺪﺷﺍﺪﺟﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻪﻛ ﻥﺎﻳﻼﺘﺒﻣﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣﻩﺮﻴﭙﺳﺁﺯﺍﻩﺪﺷﺍﺪﺟﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻭﻞﺳﺎﻤﺳﻼﭘ

.ﺪﻨﻨﻛﻲﻣﻥﺎﻴﺑﺍﺭ RANKﻝﻮﻜﻟﻮﻣﺎﻣﻮﻠﻳﺎﻣﻪﺑ

RANKﻝﻮﻜﻟﻮﻣﻥﺎﻴﺑﻲﺳﺭﺮﺑﻡﺎﺠﻧﺍﺯﺍﻲﺷﺭﺍﺰﮔﺯﻭﺮﻣﺍﻪﺑﺎﺗﻦﻴﻨﭼﻢﻫ

-ﺭﺩ .ﺖﺳﺍﻩﺪﻳﺩﺮﮕﻧﺮﺸﺘﻨﻣﻥﺎﺴﻧﺍﻭﺵﻮﻣﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻱﺎﻫﻩﺩﺭﻂﺳﻮﺗ

ﻂﺳﻮﺗRANKﻝﻮﻜﻟﻮﻣﻥﺎﻴﺑRT-PCRﺵﻭﺭﺯﺍﻩﺩﺎﻔﺘﺳﺍﺎﺑﺮﺿﺎﺣﻪﻌﻟﺎﻄﻣ ﺞﻳﺎﺘﻧ .ﺖﻓﺮﮔﺭﺍﺮﻗﻲﺑﺎﻳﺯﺭﺍﺩﺭﻮﻣU-266ﻲﻧﺎﺴﻧﺍﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭ ﺩﻮﺧﻩﺪﻧﺮﻴﮔ،RANKLﺮﺑﻩﻭﻼﻋ U-266ﻪﻛﺪﻫﺩﻲﻣﻥﺎﺸﻧﺮﺿﺎﺣﻪﻌﻟﺎﻄﻣ .ﺪﻨﻛﻲﻣﻥﺎﻴﺑﺰﻴﻧﺍﺭ (RANK)

ﻞﻴﻟﺩﻪﺑﺪﻧﺍﻮﺗﻲﻣ،RANKLﻥﺎﻴﺑﻲﺑﺎﻳﺯﺭﺍﻪﺑﻁﻮﺑﺮﻣﻱﺎﻫﻪﺘﻓﺎﻳﺭﺩﺕﻭﺎﻔﺗﻦﻳﺍ ﻱﺎﻫﺮﻤﻳﺍﺮﭘﺯﺍﻩﺩﺎﻔﺘﺳﺍﺭﺩﺎﻳﻭﺕﻭﺎﻔﺘﻣﻱﺎﻫﺖﻴﺳﺎﺴﺣﺎﺑﻲﻳﺎﻫﺵﻭﺭﺯﺍﻩﺩﺎﻔﺘﺳﺍ

RANKﻥﺎﻴﺑ .ﺯﺭﺎﮔﺁﻝژﻱﻭﺭﺮﺑﻞﺳﺎﻤﺳﻼﭘﻲﻤﺳﻮﻟﻭﺎﻣﻮﻠﻳﺎﻣﻞﭙﻴﺘﻟﺎﻣﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑﺭﺩ RANKﻱﺎﻫﺮﻤﻳﺍﺮﭘﺎﺑ PCRﺞﻳﺎﺘﻧ :3 ﻞﻜﺷ .ﺖﺳﺍﻩﺪﺷﻩﺩﺍﺩﻥﺎﺸﻧﺯﺭﺎﮔﺁﻝژﺭﺩﺯﺎﺑﺖﻔﺟ 193 ﻩﺯﺍﺪﻧﺍﺎﺑﺺﺨﺸﻣﻱﺎﻫﺪﻧﺎﺑﺕﺭﻮﺻﻪﺑﺎﻫﻞﺳﺎﻤﺳﻼﭘﻂﺳﻮﺗ

RANKLﻥﺎﻴﺑ .ﺯﺭﺎﮔﺁﻝژﻱﻭﺭﺮﺑHelaﻭU-266،-8866 RPMI ،U-937ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭﺭﺩ RANKLﻱﺎﻫﺮﻤﻳﺍﺮﭘﺎﺑ PCRﺞﻳﺎﺘﻧ :4 ﻞﻜﺷ

.ﺖﺳﺍﻩﺪﺷﻩﺩﺍﺩﻥﺎﺸﻧﺯﺎﺑﺖﻔﺟ 143 ﻩﺯﺍﺪﻧﺍﺎﺑﺕﺭﻮﺻﻪﺑﻲﻟﻮﻠﺳﻱﺎﻫﻩﺩﺭﻂﺳﻮﺗ

(6)

،ﻲﻤﻴﺷﻮﺘﺴﻴﻫﻮﻧﻮﻤﻳﺍﺵﻭﺭﺎﺑﻲﺑﺎﻳﺯﺭﺍﺭﺩﻝﺎﺜﻣﻥﺍﻮﻨﻋﻪﺑ .ﺪﺷﺎﺑﻥﻮﮔﺎﻧﻮﮔ

ﻝﻮﻜﻟﻮﻣﻪﺘﻴﺴﻴﻧژﻲﺘﻧﺁﺕﺭﺪﻗﺶﻫﺎﻛﺚﻋﺎﺑﺪﻧﺍﻮﺗﻲﻣﺖﻓﺎﺑﻥﺩﺮﻛﻪﻴﻔﻴﺴﻠﻛﺩ ﻢﻴﻘﺘﺴﻣﺕﺭﻮﺻﻪﺑﺪﻧﺍﻮﺗﻲﻣﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﺎﻳﺁﻪﻛﻪﺘﻜﻧﻦﻳﺍ .ﺩﻮﺷ RANKL ﻢﻴﻈﻨﺗﻡﺪﻋﻥﺁﺐﻗﺎﻌﺘﻣﻭﻥﺍﻮﺨﺘﺳﺍﺰﻐﻣ OPGﻭ RANKLﺮﻳﺩﺎﻘﻣﻢﻴﻈﻨﺗﺭﺩ ﻚﻳﺕﺭﻮﺻﻪﺑﻪﺸﻴﻤﻫ،ﺪﺷﺎﺑﻪﺘﺷﺍﺩﺶﻘﻧﻥﺍﻮﺨﺘﺳﺍﺐﻳﺮﺨﺗﻭﻱﺯﺎﺳﻮﻧﻪﺳﻭﺮﭘ

.ﺖﺳﺍﻩﺩﻮﺑﺡﺮﻄﻣﺰﻴﮕﻧﺍﺮﺑﺚﺤﺑﻉﻮﺿﻮﻣ

ﻥﺎﻴﺑ ﻲﺑﺎﻳﺯﺭﺍ ﻪﺑ RT-PCRﺵﻭﺭﺯﺍ ﻩﺩﺎﻔﺘﺳﺍﺎﺑ ﺮﺿﺎﺣﻪﻌﻟﺎﻄﻣ ﺭﺩ

ﻭ U-266ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭﻂﺳﻮﺗ RANKLﻭ RANKﻱﺎﻫﻝﻮﻜﻟﻮﻣ

ﻲﻤﺳﻮﻟﻭﺎﻣﻮﻠﻳﺎﻣﻪﺑﻥﺎﻳﻼﺘﺒﻣﻲﻄﻴﺤﻣﻥﻮﺧﻭﻩﺮﻴﭙﺳﺁﺯﺍﻩﺪﺷﺍﺪﺟﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘ ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭﻪﻛﺪﺷﻩﺩﺍﺩﻥﺎﺸﻧﻪﻌﻟﺎﻄﻣﻦﻳﺍﺭﺩ .ﺪﺷﻪﺘﺧﺍﺩﺮﭘﻞﺳﺎﻤﺳﻼﭘ

ﺍﺭ RANKﻝﻮﻜﻟﻮﻣﻥﺍﺭﺎﻤﻴﺑﻪﻧﻮﻤﻧﺯﺍﻩﺪﺷﺍﺪﺟﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻭ U-266

RT-PCRﺵﻭﺭﺯﺍﻩﺩﺎﻔﺘﺳﺍﺎﺑﻦﻳﺍﺮﺑﻩﻭﻼﻋ .ﺪﻨﻨﻛﻲﻣﻥﺎﻴﺑ mRNAﺢﻄﺳ

ﻉﻮﻧﻭﺩﺮﻫﻲﻳﺎﺳﺎﻨﺷﻪﺑﺭﺩﺎﻗﻪﻛﻲﺗﺭﻮﺻﻪﺑ RANKLﻱﺎﻫﺮﻤﻳﺍﺮﭘﻲﺣﺍﺮﻃﻭ ﺞﻳﺎﺘﻧﻭﺖﻓﺮﮔﺭﺍﺮﻗﻲﺑﺎﻳﺯﺭﺍﺩﺭﻮﻣﻝﻮﻜﻟﻮﻣﻦﻳﺍﻥﺎﻴﺑ،ﺪﻨﺷﺎﺑ RANKLﻡﺮﻓﻭﺰﻳﺍ ﻩﺪﺷﺍﺪﺟﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﻭ U-266ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭﻪﻛﺩﺍﺩﻥﺎﺸﻧﻞﺻﺎﺣ .ﺪﻨﻨﻛﻲﻣﻥﺎﻴﺑﺰﻴﻧﺍﺭ RANKLﻝﻮﻜﻟﻮﻣﻲﻳﺎﻣﻮﻠﻳﺎﻣﻥﺍﺭﺎﻤﻴﺑﻪﻧﻮﻤﻧﺯﺍ ﻱﺪﻨﻤﺷﺯﺭﺍﺭﺎﻴﺴﺑﻪﺘﻓﺎﻳﺪﻧﺍﻮﺗﻲﻣﻲﺳﺭﺮﺑﻦﻳﺍﺯﺍﻞﺻﺎﺣﺞﻳﺎﺘﻧ،ﻞﻛﺭﺩ ﺭﺩﻥﺍﻮﺨﺘﺳﺍﻚﻴﺘﻴﻟﺕﺎﻌﻳﺎﺿﻭﻥﺍﻮﺨﺘﺳﺍﻱﺭﺎﻤﻴﺑﺲﻳﺰﻧژﻮﺗﺎﭘﺮﺗﻖﻴﻗﺩﻢﻬﻓﺭﺩ ﻥﺍﻮﺨﺘﺳﺍﻱﺮﻴﮔﺭﺩﻪﻛﺪﺷﺎﺑﻱﺮﮕﻳﺩﻱﺎﻫﻲﻤﻴﺧﺪﺑﻻﺎﻤﺘﺣﺍﻭﺎﻣﻮﻠﻳﺎﻣﻪﺑﻥﺎﻳﻼﺘﺒﻣ

RT-PCRﺵﻭﺭﺯﺍﻩﺩﺎﻔﺘﺳﺍﺎﺑﻲﺳﺭﺮﺑﻦﻳﺍﺭﺩﺍﺮﻳﺯ،ﺖﺳﺍﻲﻌﻳﺎﺷﻪﺘﻓﺎﻳﺎﻬﻧﺁﺭﺩ

ﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘﺰﻴﻧﻭﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﻩﺩﺭﺭﺩ،RANKLﻥﺎﻴﺑﻭRANKﻥﺎﻴﺑ .ﺖﺳﺍﻪﺘﻓﺮﮔﺭﺍﺮﻗﻲﺑﺎﻳﺯﺭﺍﺩﺭﻮﻣﻲﻳﺎﻣﻮﻠﻳﺎﻣﻥﺍﺭﺎﻤﻴﺑﻪﻧﻮﻤﻧﺯﺍﻩﺪﺷﺍﺪﺟ

ﻱﺮﻴﮔ

ﻪﺠﻴﺘﻧ

ﺎﻣﻮﻠﻳﺎﻣﻪﺑﻼﺘﺒﻣﻥﺍﺭﺎﻤﻴﺑﺭﺩﻪﻜﻨﻳﺍﺮﺑﺪﻨﻛﻲﻣﺖﻟﻻﺩﺎﻣﻱﺎﻫﻪﺘﻓﺎﻳ،ﻉﻮﻤﺠﻣﺭﺩ ﺎﻬﻧﺁﻪﺑﻞﻳﺫﺭﺩﻪﻛﻲﺗﻻﺎﻤﺘﺣﺍﻖﻳﺮﻃﺯﺍﺪﻨﻧﺍﻮﺗﻲﻣﻝﺎﻧﻮﻠﻛﻮﻧﻮﻣﻱﺎﻫﻞﺳﺎﻤﺳﻼﭘ ﻥﺁﺐﻗﺎﻌﺘﻣﻭ Bone-remodelingﻪﺳﻭﺮﭘﻢﻴﻈﻨﺗﻡﺪﻋﺚﻋﺎﺑ،ﺖﺳﺍﻩﺪﺷﻩﺭﺎﺷﺍ :ﺪﻧﻮﺸﺑﻥﺍﻮﺨﺘﺳﺍﺐﻳﺮﺨﺗﺶﻳﺍﺰﻓﺍﻭﺎﻫﺖﺳﻼﻛﻮﺌﺘﺳﺍﺖﻴﻟﺎﻌﻓﺶﻳﺍﺰﻓﺍ

ﺎﻫﻞﺳﺎﻤﺳﻼﭘﻂﺳﻮﺗ RANKLﺢﺷﺮﺗﻭﺪﻴﻟﻮﺗ

-ﺎﻫﻞﺳﺎﻤﺳﻼﭘﻂﺳﻮﺗ RANKﺪﻴﻟﻮﺗ

-ﺖﺳﻼﻛﻮﺌﺘﺳﺍﺭﺩ RANK/RANKLﻡﺎﻴﭘﻝﺎﻘﺘﻧﺍﺮﻴﺴﻣﺖﻴﻟﺎﻌﻓﺶﻳﺍﺰﻓﺍ

-ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻝﻮﻠﺳﺭﺩ RANK/RANKLﻡﺎﻴﭘﻝﺎﻘﺘﻧﺍﺮﻴﺴﻣﺖﻴﻟﺎﻌﻓﺶﻳﺍﺰﻓﺍ

-ﻲﻳﺎﻣﻮﻠﻳﺎﻣﻥﺍﺭﺎﻤﻴﺑﺭﺩ OPGﻥﺎﻴﺑﺶﻫﺎﻛ

-ﺮﻜﺸﺗ

ﻭ

ﺮﻳﺪﻘﺗ

ﻲﺸﻫﻭﮋﭘ ﺖﻧﻭﺎﻌﻣ ﻂﺳﻮﺗ ﻲﺗﺎﻘﻴﻘﺤﺗ ﺡﺮﻃ ﻦﻳﺍ ﻪﺑ ﻁﻮﺑﺮﻣ ﻱﺎﻫﻪﻨﻳﺰﻫ ﺯﺍ ﺍﺬﻟ .ﺪﺷ ﺖﺧﺍﺩﺮﭘ ﺱﺭﺪﻣ ﺖﻴﺑﺮﺗ ﻩﺎﮕﺸﻧﺍﺩﻲﻜﺷﺰﭘ ﻡﻮﻠﻋﻩﺪﻜﺸﻧﺍﺩ .ﺩﻮﺷﻲﻣﻲﻧﺍﺩﺭﺪﻗﻭﺮﻜﺸﺗﺰﻛﺮﻣﻦﻳﺍﻱﺭﺎﻜﻤﻫ

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