Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis.
Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis.
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DOI：
10.1126/scitranslmed.3002214
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发表时间：
2011-09-21
影响因子：
17.1
通讯作者：
Zuscik MJ
中科院分区：
文献类型：
--
作者：
Sampson ER;Hilton MJ;Tian Y;Chen D;Schwarz EM;Mooney RA;Bukata SV;O'Keefe RJ;Awad H;Puzas JE;Rosier RN;Zuscik MJ
There is no disease-modifying therapy for osteoarthritis, a degenerative joint disease that is projected to afflict more than 67 million individuals in the US alone by 2030. As disease pathogenesis is associated with inappropriate articular chondrocyte maturation resembling that seen during normal endochondral ossification, pathways that govern the maturation of these cells are candidate therapeutic targets. It is well established that parathyroid hormone (PTH) induces matrix synthesis and suppresses maturation of chondrocytes via the type 1 PTH receptor. We have found that the PTH receptor is up-regulated in articular chondrocytes following meniscal injury and during osteoarthritis in humans and in a mouse model of injury-induced knee osteoarthritis. Thus, we hypothesized that recombinant human PTH(1–34) (teriparatide) would inhibit aberrant chondrocyte maturation and associated articular cartilage degeneration. To test this, we administered systemic teriparatide (Forteo), an FDA-approved treatment for osteoporosis, either immediately after or 8 weeks after meniscal/ligamentous injury in mice. Knee joints were harvested at 4, 8, or 12 weeks post-injury to examine the effects of teriparatide on cartilage degeneration and articular chondrocyte maturation. Confirming successful systemic delivery of the drug, micro-computed tomography revealed increased bone volume within joints from teriparatide-treated mice compared to saline-treated controls. Immediate systemic administration of teriparatide increased proteoglycan content and inhibited articular cartilage degeneration, whereas delayed treatment beginning 8 weeks post-injury induced a regenerative effect. The chondro-protective and chondro-regenerative effects of teriparatide correlated with decreased levels of type × collagen, Runx2, matrix metalloproteinase-13 and the c-terminal aggrecan cleavage product NITEGE. These preclinical findings provide proof-of-concept that teriparatide (Forteo) may be useful for decelerating cartilage degeneration and inducing matrix regeneration in osteoarthritis patients.
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影响因子：
--
作者：
Hootman, JM;Helmick, CG
通讯作者：
Helmick, CG
影响因子：
--
作者：
Chen, Xuesong;Macica, Carolyn M.;Nasiri, Ali;Broadus, Arthur E.
通讯作者：
Broadus, Arthur E.
DOI：
10.1016/j.berh.2009.08.008
发表时间：
2010-02-01
影响因子：
5.2
作者：
Englund, Martin
通讯作者：
Englund, Martin
影响因子：
7
作者：
Chockalingam, P. S.;Sun, W.;Morris, E. A.
通讯作者：
Morris, E. A.
影响因子：
158.5
作者：
Felson, DT
通讯作者：
Felson, DT