PMID- 25377946
OWN - NLM
STAT- MEDLINE
DCOM- 20150720
LR  - 20181202
IS  - 1471-2474 (Electronic)
IS  - 1471-2474 (Linking)
VI  - 15
DP  - 2014 Nov 6
TI  - Effects of pamidronate disodium on the loss of osteoarthritic subchondral bone 
      and the expression of cartilaginous and subchondral osteoprotegerin and RANKL in 
      rabbits.
PG  - 370
LID - 10.1186/1471-2474-15-370 [doi]
LID - 370
AB  - BACKGROUND: Osteoarthritis (OA) is a major health problem in the increasingly 
      elderly population. Therefore, it is crucial to prevent and treat OA at an early 
      stage. The present study investigated whether pamidronate disodium (PAM), a 
      bone-loss inhibitor, can significantly prevent or reverse the progression of 
      early anterior cruciate ligament transection (ACLT)-induced OA. Whether 
      therapeutic intervention is associated with regulation of the expression of 
      osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), 
      metalloproteinase-9 (MMP-9) or Toll-like receptor-4 (TLR-4) in cartilage and/or 
      subchondral bone was also investigated. METHODS: 60 New Zealand rabbits were 
      randomized into four groups: Sham-operated (n = 20); ACLT (n = 20); short-term 
      treatment with PAM (PAM-S, n = 10) and long-term treatment with PAM (PAM-L, n = 
      10). For cartilage and subchondral bone testing, rabbits from Sham and ACLT 
      groups were harvested at 2, 4, 6, and 14 weeks. Rabbits were given PAM from the 
      4th week after ACLT operation in PAM-S and PAM-L group, and were harvested at 6 
      and 14 weeks, respectively. Trabecular characteristics and cartilage changes were 
      detected using Micro-CT, safranin O and rapid green staining, respectively. 
      Immunohistochemical staining for OPG and RANKL were also performed. OPG, RANKL, 
      MMP-9 and TLR-4 expression was evaluated by western blot analysis. RESULTS: 
      Micro-CT and histology analyses indicated that PAM treatment for 2 or 10 weeks 
      could completely prevent or reverse osteoarthritic subchondral bone loss and 
      cartilage surface erosion. Immunohistochemistry and western blot analysis 
      indicated that expression of OPG and RANKL increased, although RANKL expression 
      increased more significantly than that of OPG. Therefore the ratio of OPG to 
      RANKL was lower in the ACLT group. However, the ratio of OPG to RANKL in the PAM 
      group was significantly higher than that in the ACLT group. Additionally, 
      expression of MMP-9 and TLR-4 were upregulated in the ACLT group and 
      downregulated in the PAM treated groups. CONCLUSIONS: PAM can significantly 
      inhibit and even reverse early osteoarthritic subchondral bone loss, thus 
      alleviating the process of cartilaginous degeneration. The mechanisms involved 
      may be associated with the upregulation of OPG expression, and downregulation of 
      RANKL, MMP-9 and TLR-4 expression.
FAU - Lv, You
AU  - Lv Y
FAU - Xia, Jie-yun
AU  - Xia JY
FAU - Chen, Jing-yang
AU  - Chen JY
FAU - Zhao, Hui
AU  - Zhao H
FAU - Yan, Hai-cui
AU  - Yan HC
FAU - Yang, Han-shi
AU  - Yang HS
FAU - Li, Qiang
AU  - Li Q
FAU - Fan, Yu-xin
AU  - Fan YX
FAU - Guo, Kai-jin
AU  - Guo KJ
AD  - Department of Orthopedics, Affiliated Hospital of Xuzhou Medical University, 99 
      Huaihai Road, Xuzhou 221002, Jiangsu, China. Xzgkj@sina.com.
FAU - Chen, Xiang-yang
AU  - Chen XY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141106
PL  - England
TA  - BMC Musculoskelet Disord
JT  - BMC musculoskeletal disorders
JID - 100968565
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Diphosphonates)
RN  - 0 (Osteoprotegerin)
RN  - 0 (RANK Ligand)
RN  - OYY3447OMC (Pamidronate)
SB  - IM
MH  - Animals
MH  - Bone Density Conservation Agents/pharmacology/therapeutic use
MH  - Cartilage, Articular/drug effects/*metabolism
MH  - Diphosphonates/pharmacology/*therapeutic use
MH  - Gene Expression Regulation
MH  - Osteoarthritis/*drug therapy/*metabolism
MH  - Osteoprotegerin/*biosynthesis
MH  - Pamidronate
MH  - RANK Ligand/*biosynthesis
MH  - Rabbits
MH  - Random Allocation
MH  - Treatment Outcome
PMC - PMC4240862
EDAT- 2014/11/08 06:00
MHDA- 2015/07/21 06:00
PMCR- 2014/11/06
CRDT- 2014/11/08 06:00
PHST- 2014/07/10 00:00 [received]
PHST- 2014/10/20 00:00 [accepted]
PHST- 2014/11/08 06:00 [entrez]
PHST- 2014/11/08 06:00 [pubmed]
PHST- 2015/07/21 06:00 [medline]
PHST- 2014/11/06 00:00 [pmc-release]
AID - 1471-2474-15-370 [pii]
AID - 2308 [pii]
AID - 10.1186/1471-2474-15-370 [doi]
PST - epublish
SO  - BMC Musculoskelet Disord. 2014 Nov 6;15:370. doi: 10.1186/1471-2474-15-370.