Mice lacking pten in osteoblasts have improved intramembranous and late endochondral fracture healing.
Mice lacking pten in osteoblasts have improved intramembranous and late endochondral fracture healing.
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DOI：
10.1371/journal.pone.0063857
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Williams BO
中科院分区：
文献类型：
--
作者：
Burgers TA;Hoffmann MF;Collins CJ;Zahatnansky J;Alvarado MA;Morris MR;Sietsema DL;Mason JJ;Jones CB;Ploeg HL;Williams BO
骨折愈合失败（骨不连的发展）是一个常见的和使人衰弱的临床问题。在成骨细胞中缺乏肿瘤抑制因子Pten的小鼠在一生中骨体积和密度显著和渐进地增加。由于骨折愈合是骨发育的重演，我们研究了成骨细胞中缺乏Pten的小鼠（Ocn-cretg/+;Ptenflox/flox）的骨折愈合过程。通过显微计算机断层扫描（µCT）扫描、生物力学测试、组织学和组织形态计量学分析以及蛋白质表达分析，研究了野生型和Ocn-cretg/+;Ptenflox/flox小鼠中诱导的股骨中段骨折。在所有队列中，Ocn-cretg/+;Ptenflox/flox小鼠相对于对照组具有显著更硬和更强的完整骨。骨折后第28天（PF），他们的愈合骨明显更硬，第14、21和28天的愈合骨明显更强。在第7天PF，Pten突变体愈伤组织的近端和远端更加骨化。到PF第28天，Pten突变体具有更大和更多矿化的愈伤组织。在愈合过程中，Pten突变体改善了源自骨膜的膜内骨形成。在愈合过程后期，在骨痂中存在成熟的成骨细胞后，它们也改善了软骨内骨形成。我们的研究结果表明，抑制Pten可以改善骨折愈合，并且局部或短期使用市售的Pten抑制剂可能具有增强骨折愈合的临床应用。
The failure of an osseous fracture to heal (development of a non-union) is a common and debilitating clinical problem. Mice lacking the tumor suppressor Pten in osteoblasts have dramatic and progressive increases in bone volume and density throughout life. Since fracture healing is a recapitulation of bone development, we investigated the process of fracture healing in mice lacking Pten in osteoblasts (Ocn-cretg/+;Ptenflox/flox). Mid-diaphyseal femoral fractures induced in wild-type and Ocn-cretg/+;Ptenflox/flox mice were studied via micro-computed tomography (µCT) scans, biomechanical testing, histological and histomorphometric analysis, and protein expression analysis. Ocn-cretg/+;Ptenflox/flox mice had significantly stiffer and stronger intact bones relative to controls in all cohorts. They also had significantly stiffer healing bones at day 28 post-fracture (PF) and significantly stronger healing bones at days 14, 21, and 28 PF. At day 7 PF, the proximal and distal ends of the Pten mutant calluses were more ossified. By day 28 PF, Pten mutants had larger and more mineralized calluses. Pten mutants had improved intramembranous bone formation during healing originating from the periosteum. They also had improved endochondral bone formation later in the healing process, after mature osteoblasts are present in the callus. Our results indicate that the inhibition of Pten can improve fracture healing and that the local or short-term use of commercially available Pten-inhibiting agents may have clinical application for enhancing fracture healing.
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影响因子：
5.6
作者：
Gaur, Tripti;Wixted, John J.;Hussain, Sadiq;O'Connell, Shannon L.;Morgan, Elise F.;Ayers, David C.;Komm, Barry S.;Bodine, Peter V.;Stein, Gary S.;Lian, Jane B.
通讯作者：
Lian, Jane B.
DOI：
10.1615/critreveukargeneexpr.v20.i2.20
发表时间：
2010
影响因子：
1.6
作者：
Coulibaly MO;Sietsema DL;Burgers TA;Mason J;Williams BO;Jones CB
通讯作者：
Jones CB
影响因子：
3.1
作者：
Hugunin, Kelly M. S.;Fry, Christopher;Nemzek, Jean A.
通讯作者：
Nemzek, Jean A.
DOI：
10.1097/ta.0b013e3181469840
发表时间：
2008-06-01
影响因子：
--
作者：
Court-Brown, Charles M.;McQueen, Margaret M.
通讯作者：
McQueen, Margaret M.
影响因子：
2.8
作者：
Komatsu, David E.;Mary, Michelle N.;Schroeder, Robert Jason;Robling, Alex G.;Turner, Charles H.;Warden, Stuart J.
通讯作者：
Warden, Stuart J.