Hara Emilio Satoshi, Okada Masahiro, Nagaoka Noriyuki, Hattori Takako, Iida Letycia Mary, Kuboki Takuo, Nakano Takayoshi, Matsumoto Takuya
Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama-ken, 700-8525, Okayama, Japan.
Integr Biol (Camb). 2018 Jan 22;10(1):57-66. doi: 10.1039/c7ib00130d.
Analysis of tissue development from multidisciplinary approaches can result in more integrative biological findings, and can eventually allow the development of more effective bioengineering methods. In this study, we analyzed the initial steps of mineral formation during secondary ossification of mouse femur based on biological and bioengineering approaches. We first found that some chondrocytes burst near the mineralized area. External factors that could trigger chondrocyte burst were then investigated. Chondrocyte burst was shown to be modulated by mechanical and osmotic pressure. A hypotonic solution, as well as mechanical stress, significantly induced chondrocyte burst. We further hypothesized that chondrocyte burst could be associated with space-making for mineral expansion. In fact, ex vivo culture of femur epiphysis in hypotonic conditions, or under mechanical pressure, enhanced mineral formation, compared to normal culture conditions. Additionally, the effect of mechanical pressure on bone formation in vivo was investigated by immobilization of mouse lower limbs to decrease the body pressure onto the joints. The results showed that limb immobilization suppressed bone formation. Together, these results suggest chondrocyte burst as a novel fate of chondrocytes, and that manipulation of chondrocyte burst with external mechano-chemical stimuli could be an additional approach for cartilage and bone tissue engineering.
从多学科方法分析组织发育可以产生更综合的生物学发现，并最终促进更有效的生物工程方法的发展。在本研究中，我们基于生物学和生物工程方法分析了小鼠股骨二次骨化过程中矿物质形成的初始步骤。我们首先发现一些软骨细胞在矿化区域附近破裂。然后研究了可能触发软骨细胞破裂的外部因素。结果表明，软骨细胞破裂受机械压力和渗透压调节。低渗溶液以及机械应力均能显著诱导软骨细胞破裂。我们进一步推测，软骨细胞破裂可能与为矿物质扩张创造空间有关。事实上，与正常培养条件相比，在低渗条件下或机械压力下对股骨骨骺进行体外培养可增强矿物质形成。此外，通过固定小鼠下肢以降低关节上的身体压力，研究了机械压力对体内骨形成的影响。结果表明，肢体固定会抑制骨形成。综上所述，这些结果表明软骨细胞破裂是软骨细胞的一种新命运，并且利用外部机械化学刺激来操纵软骨细胞破裂可能是软骨和骨组织工程的一种额外方法。
