Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model
Abstract
De-gang YU1, #, Hui-feng DING1, #, Yuan-qing MAO1, *, Ming LIU1, Bo YU2, Xin ZHAO1, Xiao-qing WANG1, Yang LI1, Guang-wang LIU1, Shao-bo NIE3, Shen LIU4, Zhen-an ZHU1
1Department of Orthopedics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China; 2Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji-nan 250014, China; 3Department of Orthopedics, PLA General Hospital, Beijing 100853, China; 4Department of Orthopedics, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China
Aim: To investigate whether strontium ranelate (SR), a new antiosteoporotic agent, could attenuate cartilage degeneration and subchondral bone remodeling in osteoarthritis (OA).
Methods: Medial meniscal tear (MMT) operation was performed in adult SD rats to induce OA. SR (625 or 1800 mg·kg-1·d-1) was administered via gavage for 3 or 6 weeks. After the animals were sacrificed, articular cartilage degeneration was evaluated using toluidine blue O staining, SOX9 immunohistochemistry and TUNEL assay. The changes in microarchitecture indices and tissue mineral density (TMD), chemical composition (mineral-to-collagen ratio), and intrinsic mechanical properties of the subchondral bones were measured using micro-CT scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively.
Results: The high-dose SR significantly attenuated cartilage matrix and chondrocyte loss at 6 weeks, and decreased chondrocyte apoptosis, improved the expression of SOX9, a critical transcription factor responsible for the expression of anabolic genes type II collagen and aggrecan, at both 3 and 6 weeks. Meanwhile, the high-dose SR also significantly attenuated the subchondral bone remodeling at both 3 and 6 weeks, as shown by the improved microarchitecture indices, TMD, mineral-to-collagen ratio and intrinsic mechanical properties. In contrast, the low-dose SR did not significantly change all the detection indices of cartilage and bone at both 3 and 6 weeks.
Conclusion: The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA.
Keywords: osteoarthritis; antiosteoporotic agent; strontium ranelate; medial meniscal tear; articular cartilage; subchondral bone; SOX9
This work was supported by grants from the National Natural Science Foundation of China (No 30700852, 30973038), the Fund for Key Disciplines of Shanghai Municipal Education Commission (J50206) and the Program for the Shanghai Key Laboratory of Orthopedic Implants (Grant No 08DZ2230330).
# The two authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail yuanqingmao@163.com
Received 2012-06-24 Accepted 2012-11-14
Keywords:
1Department of Orthopedics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China; 2Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji-nan 250014, China; 3Department of Orthopedics, PLA General Hospital, Beijing 100853, China; 4Department of Orthopedics, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China
Aim: To investigate whether strontium ranelate (SR), a new antiosteoporotic agent, could attenuate cartilage degeneration and subchondral bone remodeling in osteoarthritis (OA).
Methods: Medial meniscal tear (MMT) operation was performed in adult SD rats to induce OA. SR (625 or 1800 mg·kg-1·d-1) was administered via gavage for 3 or 6 weeks. After the animals were sacrificed, articular cartilage degeneration was evaluated using toluidine blue O staining, SOX9 immunohistochemistry and TUNEL assay. The changes in microarchitecture indices and tissue mineral density (TMD), chemical composition (mineral-to-collagen ratio), and intrinsic mechanical properties of the subchondral bones were measured using micro-CT scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively.
Results: The high-dose SR significantly attenuated cartilage matrix and chondrocyte loss at 6 weeks, and decreased chondrocyte apoptosis, improved the expression of SOX9, a critical transcription factor responsible for the expression of anabolic genes type II collagen and aggrecan, at both 3 and 6 weeks. Meanwhile, the high-dose SR also significantly attenuated the subchondral bone remodeling at both 3 and 6 weeks, as shown by the improved microarchitecture indices, TMD, mineral-to-collagen ratio and intrinsic mechanical properties. In contrast, the low-dose SR did not significantly change all the detection indices of cartilage and bone at both 3 and 6 weeks.
Conclusion: The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA.
Keywords: osteoarthritis; antiosteoporotic agent; strontium ranelate; medial meniscal tear; articular cartilage; subchondral bone; SOX9
This work was supported by grants from the National Natural Science Foundation of China (No 30700852, 30973038), the Fund for Key Disciplines of Shanghai Municipal Education Commission (J50206) and the Program for the Shanghai Key Laboratory of Orthopedic Implants (Grant No 08DZ2230330).
# The two authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail yuanqingmao@163.com
Received 2012-06-24 Accepted 2012-11-14