Targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism.
Targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism.
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DOI：
10.1371/journal.pone.0033543
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cohen-Solal ME
中科院分区：
文献类型：
--
作者：
Funck-Brentano T;Lin H;Hay E;Ah Kioon MD;Schiltz C;Hannouche D;Nizard R;Lioté F;Orcel P;de Vernejoul MC;Cohen-Solal ME
软骨下骨改变发生在骨关节炎（OA）发展的早期。骨吸收水平可能影响软骨重塑。因此，我们评估了骨吸收和软骨代谢的体内和体外靶向作用。在用雌二醇（E2）、帕米膦酸盐（PAM）或磷酸盐缓冲盐水（PBS）治疗6周的去卵巢骨质减少小鼠（OP）中，通过卵巢切除术（MNX）诱导OA。我们评估了软骨下骨和软骨结构以及软骨基质蛋白酶的表达。为了评估骨可溶性因子在软骨代谢中的参与，将用E2或PAM预处理的人骨外植体的上清液转移至软骨外植体以评估蛋白聚糖释放和聚集蛋白聚糖裂解。通过实时定量PCR评估骨外植体中OPG/RANKL mRNA的表达。骨保护素（OPG）在骨软骨串扰的作用进行了测试，使用OPG中和抗体。E2和PAM可使OP小鼠的骨密度和破骨细胞数恢复（p<0.05）。在OP小鼠中，E2和PAM降低ADAMTS-4和-5表达，而与PBS相比，仅PAM显著降低OA（2.0±0.63 vs 5.2±0.95; p<0.05）。OPG/RANKL mRNA在两种药物处理的人骨外植体中均增加（2.2-3.7倍）。此外，来自与E2或PAM一起培养的骨外植体的上清液减少聚集蛋白聚糖切割和软骨蛋白聚糖释放（分别为对照的73±8.0%和80±22%，p<0.05）。这种作用被骨保护素阻断剂逆转。帕米膦酸盐对骨质减少小鼠骨吸收的抑制作用使组织学OA评分降低，聚集蛋白聚糖酶表达减少。骨可溶性因子，如骨保护素，影响软骨对分解代谢因子的反应。这项研究进一步强调了软骨下骨在OA关节软骨损伤调节中的重要性。
Subchondral bone modifications occur early in the development of osteoarthritis (OA). The level of bone resorption might impact cartilage remodeling. We therefore assessed the in vivo and in vitro effects of targeting bone resorption in OA and cartilage metabolism. OA was induced by meniscectomy (MNX) in ovariectomized osteopenic mice (OP) treated with estradiol (E2), pamidronate (PAM), or phosphate buffered saline (PBS) for 6 weeks. We assessed the subchondral bone and cartilage structure and the expression of cartilage matrix proteases. To assess the involvement of bone soluble factors in cartilage metabolism, supernatant of human bone explants pre-treated with E2 or PAM were transferred to cartilage explants to assess proteoglycan release and aggrecan cleavage. OPG/RANKL mRNA expression was assessed in bone explants by real-time quantitative PCR. The role of osteoprotegerin (OPG) in the bone-cartilage crosstalk was tested using an OPG neutralizing antibody. Bone mineral density of OP mice and osteoclast number were restored by E2 and PAM (p<0.05). In OP mice, E2 and PAM decreased ADAMTS-4 and -5 expression, while only PAM markedly reduced OA compared to PBS (2.0±0.63 vs 5.2±0.95; p<0.05). OPG/RANKL mRNA was increased in human bone explants treated with both drugs (2.2–3.7-fold). Moreover, supernatants from bone explants cultured with E2 or PAM reduced aggrecan cleavage and cartilage proteoglycan release (73±8.0% and 80±22% of control, respectively, p<0.05). This effect was reversed with osteoprotegerin blockade. The inhibition of bone resorption by pamidronate in osteopenic mice alleviates the histological OA score with a reduction in the expression of aggrecanases. Bone soluble factors, such as osteoprotegerin, impact the cartilage response to catabolic factors. This study further highlights the importance of subchondral bone in the regulation of joint cartilage damage in OA.
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影响因子：
--
作者：
Kadri, A.;Ea, H. K.;Cohen-Solal, M. E.
通讯作者：
Cohen-Solal, M. E.
影响因子：
27.4
作者：
Kadri, Abderrahim;Funck-Brentano, Thomas;Cohen-Solal, Martine E.
通讯作者：
Cohen-Solal, Martine E.
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
19.7
作者：
Crema, Michel D.;Roemer, Frank W.;Guermazi, Ali
通讯作者：
Guermazi, Ali
影响因子：
--
作者：
Moreno-Rubio, Juan;Herrero-Beaumont, Gabriel;Largo, Raquel
通讯作者：
Largo, Raquel