Premnath Priyatha, Jorgenson Britta, Hess Ricarda, Tailor Pankaj, Louie Dante, Taiani Jaymi, Boyd Steven, Krawetz Roman
McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
BMC Musculoskelet Disord. 2017 Nov 9;18(1):435. doi: 10.1186/s12891-017-1790-z.
p21, a cyclin dependent kinase inhibitor has been shown to influence cell proliferation, differentiation and apoptosis; but more recently, p21 has been implicated in tissue repair. Studies on p21() knockout mice have demonstrated results that vary from complete regeneration and healing of tissue to attenuated healing. There have however been no studies that have evaluated the role of p21 inhibition in bone healing and remodeling.
The current study employs a burr-hole fracture model to investigate bone regeneration subsequent to an injury in a p21 mouse model. p21 and C57BL/6 mice were subjected to a burr-hole fracture on their proximal tibia, and their bony parameters were measured over 4 weeks via in vivo μCT scanning.
p21 mice present with enhanced healing from week 1 through week 4. Differences in bone formation and resorption potential between the two mouse models are assessed via quantitative and functional assays. While the μCT analysis indicates that p21 mice have enhanced bone healing capabilities, it appears that the differences observed may not be due to the function of osteoblasts or osteoclasts. Furthermore, no differences were observed in the differentiation of progenitor cells (mesenchymal or monocytic) into osteoblasts or osteoclasts respectively.
Therefore, it remains unknown how p21 is regulating enhanced fracture repair and further studies are required to determine which cell type(s) are responsible for this regenerative phenotype.
p21是一种细胞周期蛋白依赖性激酶抑制剂,已被证明可影响细胞增殖、分化和凋亡;但最近,p21与组织修复有关。对p21基因敲除小鼠的研究结果各不相同,从组织的完全再生和愈合到愈合减弱。然而,尚无研究评估p21抑制在骨愈合和重塑中的作用。
本研究采用钻孔骨折模型,在p21小鼠模型中研究损伤后的骨再生情况。对p21小鼠和C57BL/6小鼠的胫骨近端进行钻孔骨折,并通过体内微计算机断层扫描(μCT)在4周内测量其骨参数。
p21小鼠从第1周开始到第4周愈合增强。通过定量和功能分析评估两种小鼠模型在骨形成和吸收潜力方面的差异。虽然μCT分析表明p21小鼠具有增强的骨愈合能力,但观察到的差异似乎并非由于成骨细胞或破骨细胞的功能。此外,在祖细胞(间充质或单核细胞)分别向成骨细胞或破骨细胞的分化过程中未观察到差异。
因此,p21如何调节增强的骨折修复仍不清楚,需要进一步研究以确定哪种细胞类型导致了这种再生表型。