研究者詳細 - 窪木　拓男

Loss of oral self-care ability results in a higher risk of pneumonia in older inpatients: A prospective cohort study in a Japanese rural hospital. 国際誌

Aya Fujiwara, Hajime Minakuchi, Junji Uehara, Haruna Miki, Mami Inoue-Minakuchi, Aya Kimura-Ono, Kumiko Nawachi, Kenji Maekawa, Takuo Kuboki

Gerodontology 36 ( 3 ) 236 - 243 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

OBJECTIVES: To identify significant risk factors associated with incidence of mortality and pneumonia in whole-community-based older inpatients resident in Japanese rural region. METHODS: Patients older than 65 years admitted between 1 April and 15 April 2010 to a core hospital located in a rural region were exhaustively recruited, and incidence of mortality and pneumonia during the 32-month follow-up period were evaluated. Independent variables at baseline measurement included age, gender, body mass index, Charlson comorbidity index, functional dependency, oral self-care ability index, number of remaining teeth, hyposalivation and nutritional status. Dependent variables were incidence of mortality and pneumonia. Survival and non-pneumonia curves were drawn using Kaplan-Meier analysis. Cox proportional hazards analysis was performed to identify the risk factors related to incidence of mortality and pneumonia. RESULTS: The survival rate of 46 patients (male/female: 11/35; mean age: 83.8 ± 6.8 years) was 52.1%, and the incidence of pneumonia was 60.9%. Malnutrition and gender (male) were identified as significant risk factors for mortality (odds ratio [OR]: 8.18 and 4.90; 95% confidence interval [CI]: 1.77-37.3 and 1.50-16.0; P < 0.01 and <0.01, respectively). Loss of oral self-care ability and gender (male) were identified as significant risk factors for incidence of pneumonia (OR: 8.97 and 4.58; 95% CI: 1.70-47.4 and 1.50-14.0; P = 0.01 and <0.01, respectively). CONCLUSIONS: Malnutrition and loss of oral self-care ability were significant risk factors for incidence of mortality and pneumonia, respectively. In response, supplying nutrition with appropriate diet and personalised oral care might contribute to reduction in mortality and prevention of pneumonia.

DOI： 10.1111/ger.12402

Fibronectin-induced ductal formation in salivary gland self-organization model. 国際誌

Mahmoud Farahat, Gulsan A S Kazi, Hiroaki Taketa, Emilio S Hara, Masamitsu Oshima, Takuo Kuboki, Takuya Matsumoto

Developmental dynamics : an official publication of the American Association of Anatomists 248 ( 9 ) 813 - 825 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

BACKGROUND: Recent advances in tissue regeneration approaches including 3D organoids, were based on various 3D organogenesis models. However, 3D models are generally technique-sensitive and time-consuming. Thus, we utilized an existing model of submandibular salivary gland (SMG) to modify a simple and highly reproducible in vitro 3D culture model of primary SMG cells self-organization into a well-developed cell spheroid inside Matrigel substrate. We used this model to observe the collective multicellular behavior during spheroid formation. Further, we applied various quantitative approaches including real-time live imaging and immune histochemical image analysis to dissect the cellular dynamics during tissue patterning. RESULTS: On a time-scale of hours, we observed marked size and shape transformations in the developed 3D spheroid which resulted in a spatially-controlled growth differential from the canter to the periphery of the formed aggregates. Moreover, we investigated the effect of fibronectin (FN) on SMG cells self-organization using our simplified culture model. Interestingly, we discovered a novel role of FN in inducing duct-like elongation during initial stages of SMG bud formation. CONCLUSION: This in vitro model provides an excellent tool for analyzing the intercellular dynamics during early SMG tissue development as well as revealing a novel role of FN in SMG ductal expansion.

DOI： 10.1002/dvdy.78

Fifteen-year survival of resin-bonded vs full-coverage fixed dental prostheses. 査読

T Yoshida, Y Kurosaki, A Mine, A Kimura-Ono, T Mino, S Osaka, S Nakagawa, K Maekawa, T Kuboki, H Yatani, A Yamashita

Journal of prosthodontic research 63 ( 3 ) 374 - 382 2019年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: We clarified cumulative survival and event-free rates of resin-bonded fixed dental prostheses (RBFDPs) and compared them to those of fixed dental prostheses (FDPs) to refine risk factors for non-survival/event and use of tooth extraction after the period of non-survival/event. METHODS: Study subjects were selected among all patients who consecutively attended the Fixed Prosthodontic Clinic of Okayama University Hospital. Eligible patients were those who received 3-unit metal-framed 2-retainer (wing-wing) RBFDPs or conventional full-coverage FDPs (RBFDPs/FDPs: 129/177 prostheses). Data were analyzed by Kaplan-Meier analysis with the log-rank test, Mann-Whitney test, chi-square test, and Cox proportional hazards analysis. RESULTS: The 15-year cumulative survival rates were 66.5% for the RBFDP group and 61.6% for the FDP group, which were not significantly different (p = 0.59). The 15-year cumulative event-free rates were 53.4% for the RBFDP group and 59.2% for the FDP group, which were not significantly different (p = 0.52). No significant risk factors related to non-survival and event-free of RBFDPs/FDPs were identified in the analysis model using treatment method, sex, age, number of remaining teeth, and treatment site as explanatory variables. The number of cases in which RBFDPs/FDPs resulted in non-survival due to abutment tooth extraction was significantly lower in RBFDPs (p < 0.01). Further, the abutment tooth as a non-vital tooth was identified as a risk factor for RBFDPs/FDPs resulting in non-survival due to abutment tooth extraction. CONCLUSIONS: The present study is the first to indicate RBFDP as a prosthetic treatment option which should be selected for patients with slight or no abutment tooth decay.

DOI： 10.1016/j.jpor.2019.02.004

Biomimetic mineralization using matrix vesicle nanofragments. 査読国際誌

Yosuke Kunitomi, Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takuo Kuboki, Takayoshi Nakano, Hiroshi Kamioka, Takuya Matsumoto

Journal of biomedical materials research. Part A 107 ( 5 ) 1021 - 1030 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

In vitro synthesis of bone tissue has been paid attention in recent years; however, current methods to fabricate bone tissue are still ineffective due to some remaining gaps in the understanding of real in vivo bone formation process, and application of the knowledge in bone synthesis. Therefore, the objectives of this study were first, to perform a systematic and ultrastructural investigation of the initial mineral formation during intramembranous ossification of mouse calvaria from a material scientists' viewpoint, and to develop novel mineralization methods based on the in vivo findings. First, the very initial mineral deposition was found to occur at embryonic day E14.0 in mouse calvaria. Analysis of the initial bone formation process showed that it involved the following distinct steps: collagen secretion, matrix vesicle (MV) release, MV mineralization, MV rupture, and collagen fiber mineralization. Next, we performed in vitro mineralization experiments using MVs and hydrogel scaffolds. Intact MVs embedded in collagen gel did not mineralize, whereas, interestingly, MV nanofragments obtained by ultrasonication could promote rapid mineralization. These results indicate that mechanically ruptured MV membrane can be a promising material for in vitro bone tissue synthesis. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1021-1030, 2019.

DOI： 10.1002/jbm.a.36618

Acidic Pre-Conditioning Enhances the Stem Cell Phenotype of Human Bone Marrow Stem/Progenitor Cells. 査読国際誌

Yuri Hazehara-Kunitomo, Emilio Satoshi Hara, Mitsuaki Ono, Kyaw Thu Aung, Keiko Komi, Hai Thanh Pham, Kentaro Akiyama, Masahiro Okada, Toshitaka Oohashi, Takuya Matsumoto, Takuo Kuboki

International journal of molecular sciences 20 ( 5 ) 2019年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI

A deeper understanding of the detailed mechanism of in vivo tissue healing is necessary for the development of novel regenerative therapies. Among several external factors, environmental pH is one of the crucial parameters that greatly affects enzyme activity and cellular biochemical reactions involving tissue repair and homeostasis. In this study, in order to analyze the microenvironmental conditions during bone healing, we first measured the pH in vivo at the bone healing site using a high-resolution fiber optic pH microsensor directly in femur defects and tooth extraction sockets. The pH was shown to decrease from physiological 7.4 to 6.8 during the initial two days of healing (inflammatory phase). In the same initial stages of the inflammatory phase of the bone healing process, mesenchymal stem cells (MSCs) are known to migrate to the healing site to contribute to tissue repair. Therefore, we investigated the effect of a short-term acidic (pH 6.8) pre-treatment on the stemness of bone marrow-derived MSCs (BMSCs). Interestingly, the results showed that pre-treatment of BMSCs with acidic pH enhances the expression of stem cell markers (OCT-4, NANOG, SSEA-4), as well as cell viability and proliferation. On the other hand, acidic pH decreased BMSC migration ability. These results indicate that acidic pH during the initial stages of bone healing is important to enhance the stem cell properties of BMSCs. These findings may enable the development of novel methods for optimization of stem cell function towards tissue engineering or regenerative medicine.

DOI： 10.3390/ijms20051097

The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin. 査読

Hany Mohamed Khattab, Satoshi Kubota, Masaharu Takigawa, Takuo Kuboki, Walter Sebald

Journal of bone and mineral metabolism 37 ( 2 ) 199 - 205 2019年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER JAPAN KK

The antagonist-specific regulation in tissue engineering constitutes important attempts to achieve an improved and rapid bone regeneration by controlling the natural biological response of the natural body growth factors. L51P is molecularly engineered bone morphogentic protein-2 (BMP-2) variant with a substitution of the 51st leucine with a proline residue. L51P is deficient in BMP receptor binding, but maintains its structure and affinity for inhibitory proteins such as noggin, chordin, and gremlin. These modifications convert the BMP-2 variant L51P into a receptor-inactive inhibitor of BMP antagonists. This current approach may prevent the uncontrolled bone overgrowth using high concentration of BMPs and thus regulates the possible growth factor's high-dose side effects. Exploring of L51P biological functions is required to broad our understanding of BMP mutant biological functions and their potential clinical applications. The progress of L51P researches would hopefully lead to the development of multiple applications for using the L51P in bone and fracture healing disorders.

DOI： 10.1007/s00774-018-0925-0

Digital transfer of the subgingival contour and emergence profile of the provisional restoration to the final bone-anchored fixed restoration. 査読

Bone Marrow Cells Inhibit BMP-2-Induced Osteoblast Activity in the Marrow Environment. 国際誌

Ha Thi Nguyen, Mitsuaki Ono, Yasutaka Oida, Emilio Satoshi Hara, Taishi Komori, Kentaro Akiyama, Ha Thi Thu Nguyen, Kyaw Thu Aung, Hai Thanh Pham, Ikue Tosa, Takeshi Takarada, Koichi Matsuo, Toshihide Mizoguchi, Toshitaka Oohashi, Takuo Kuboki

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 34 ( 2 ) 327 - 332 2019年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Bone morphogenetic protein 2 (BMP-2) is widely known as a potent growth factor that promotes bone formation. However, an increasing number of studies have demonstrated side effects of BMP-2 therapy. A deeper understanding of the effect of BMP-2 on cells other than those involved directly in bone remodeling is of fundamental importance to promote a more effective delivery of BMP-2 to patients. In this study, we aimed to investigate the effect of BMP-2 in the marrow environment. First, BMP-2 adsorbed onto titanium implants was delivered at the tooth extraction socket (marrow-absent site) or in the mandible marrow of beagle dogs. BMP-2 could induce marked bone formation around the implant at the tooth extraction socket. Surprisingly, however, no bone formation was observed in the BMP-2-coated titanium implants inserted in the mandible marrow. In C57BL/6 mice, BMP-2 adsorbed in freeze-dried collagen pellets could induce bone formation in marrow-absent calvarial bone. However, similar to the canine model, BMP-2 could not induce bone formation in the femur marrow. Analysis of osteoblast differentiation using Col1a1(2.3)-GFP transgenic mice revealed a scarce number of osteoblasts in BMP-2-treated femurs, whereas in the control group, osteoblasts were abundant. Ablation of femur marrow recovered the BMP-2 ability to induce bone formation. In vitro experiments analyzing luciferase activity of C2C12 cells with the BMP-responsive element and alkaline phosphatase activity of MC3T3-E1 osteoblasts further revealed that bone marrow cells inhibit the BMP-2 effect on osteoblasts by direct cell-cell contact. Collectively, these results showed that the effect of BMP-2 in inducing bone formation is remarkably repressed by marrow cells via direct cell-cell contact with osteoblasts; this opens new perspectives on the clarification of the side-effects associated with BMP-2 application. © 2018 American Society for Bone and Mineral Research.

DOI： 10.1002/jbmr.3598

Yoko Kurosaki, Takuya Mino, Kenji Maekawa, Koji Izumi, Takuo Kuboki

Journal of prosthodontic research 63 ( 1 ) 125 - 129 2019年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: This report was written to introduce an attempt at clinical application of our newly developed digital workflow to reproduce the morphology of the subgingival contour and the emergence profile of the provisional restoration within the final bone-anchored fixed restoration, using a bounded unilateral edentulous case. METHODS: This digital workflow involves superimposition of the composite images of two specific types of working casts onto the working cast for the provisional restoration namely, a split cast screwed with a titanium base and a split cast screwed with a provisional restoration and integrating these with the whole intraoral surface image, in which the provisional restoration was present. The final restoration fabricated using this technique could be installed without any clinical problems. The results of in silico analysis revealed that the cubic volume ratio of the total discrepancy between the provisional and the final restorations was only 2.4%. Further, sufficient oral hygiene was maintained and the patient was satisfied with the outcome of the treatment. CONCLUSIONS: This technical report suggests that our newly developed digital workflow provided clinical applicability and may enable accurate transfer of the morphology of the subgingival contour and emergence profile of the provisional to the final bone-anchored fixed restoration.

DOI： 10.1016/j.jpor.2018.10.004

DNA Methylation-Based Regulation of Human Bone Marrow-Derived Mesenchymal Stem/Progenitor Cell Chondrogenic Differentiation. 査読国際誌

Yu Nomura, Emilio Satoshi Hara, Yuya Yoshioka, Há Thi Nguyen, Shuji Nosho, Taishi Komori, Kei Ishibashi, Toshitaka Oohashi, Mitsuaki Ono, Takuo Kuboki

Cells, tissues, organs 207 ( 3-4 ) 115 - 126 2019年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：KARGER

Stem cells have essential applications in in vitro tissue engineering or regenerative medicine. However, there is still a need to understand more deeply the mechanisms of stem cell differentiation and to optimize the methods to control stem cell function. In this study, we first investigated the activity of DNA methyltransferases (DNMTs) during chondrogenic differentiation of human bone marrow-derived mesenchymal stem/progenitor cells (hBMSCs) and found that DNMT3A and DNMT3B were markedly upregulated during hBMSC chondrogenic differentiation. In an attempt to understand the effect of DNMT3A and DNMT3B on the chondrogenic differentiation of hBMSCs, we transiently transfected the cells with expression vectors for the two enzymes. Interestingly, DNMT3A overexpression strongly enhanced the chondrogenesis of hBMSCs, by increasing the gene expression of the mature chondrocyte marker, collagen type II, more than 200-fold. Analysis of the methylation condition in the cells revealed that DNMT3A and DNMT3B methylated the promoter sequence of early stem cell markers, NANOG and POU5F1(OCT-4). Conversely, the suppression of chondrogenic differentiation and the increase in stem cell markers of hBMSCs were obtained by chemical stimulation with the demethylating agent, 5-azacitidine. Loss-of-function assays with siRNAs targeting DNMT3A also significantly suppressed the chondrogenic differentiation of hBMSCs. Together, these results not only show the critical roles of DNMTs in regulating the chondrogenic differentiation of hBMSCs, but also suggest that manipulation of DNMT activity can be important tools to enhance the differentiation of hBMSCs towards chondrogenesis for potential application in cartilage tissue engineering or cartilage regeneration.

DOI： 10.1159/000502885

Novel function of BMP-2 in inhibiting bone formation in marrow environment

Ha Nguyen Thi, Mitsuaki Ono, Yasutaka Oida, Emilio Satoshi Hara, Taishi Komori, Kentaro Akiyama, Ha Nguyen Thi Thu, Hai Thanh Pham, Kyawthu Aung, Toshitaka Oohashi, Takuo Kuboki

JOURNAL OF BONE AND MINERAL RESEARCH 33 338 - 338 2018年11月

Rapid bioinspired mineralization using cell membrane nanofragments and alkaline milieu. 査読国際誌

Emilio Satoshi Hara, Masahiro Okada, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto

Journal of materials chemistry. B 6 ( 38 ) 6153 - 6161 2018年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Royal Society of Chemistry ({RSC})

Bone is a sophisticated organic-inorganic hybrid material, whose formation involves a complex spatio-temporal sequence of events regulated by the cells. A deeper understanding of the mechanisms behind bone mineralization at different size scales, and using a multidisciplinary approach, may uncover novel pathways for the design and fabrication of functional bone tissue in vitro. The objectives of this study were first to investigate the environmental factors that prime initial mineralization using the secondary ossification center as an in vivo model, and then to apply the obtained knowledge for rapid in vitro synthesis of bone-like tissue. First, the direct and robust measurement of pH showed that femur epiphysis is alkaline (pH ≅ 8.5) at the initial mineral stage at post-natal day 6. We showed that the alkaline milieu is decisive not only for alkaline phosphatase activity, which precedes mineral formation at P6, but also for determining initial mineral precipitation and spherical morphology. Next, engineering approaches were used to synthesize bone-like tissue based on alkaline milieu and artificial chondrocyte membrane nanofragments, previously shown to be the nucleation site for mineral formation. Interestingly, mineralization using artificial cell membrane nanofragments was achieved in just 1 day. Finally, ex vivo culture of femur epiphysis in alkaline pH strongly induced chondrocyte burst, which was previously shown to be the origin of chondrocyte membrane nanofragments, and also enhanced mineral formation. Taken together, these findings not only shed more light on the microenvironmental conditions that prime initial bone formation in vivo, but they also show that alkaline milieu can be used as an important factor for enhancing methods for in vitro synthesis of bone tissue.

DOI： 10.1039/c8tb01544a

日本人を対象とした過去20年間の口腔インプラント治療の臨床成績に関するシステマティックレビュー

三野卓哉, 小田師巳, 園山亘, 窪木拓男

Quintessence Dental Implantology 25 ( 5 ) 0746‐0757 - 0757 2018年9月

CCN4/WISP1 controls cutaneous wound healing by modulating proliferation, migration and ECM expression in dermal fibroblasts via α5β1 and TNFα 国際誌

窪木拓男

Matrix Biology 68-69 533 - 546 2018年8月

多職種連携教育の導入・充実を目指して全国29歯科大学、歯学部多職種連携教育アンケート集計結果査読

片岡竜太, 浅沼直樹, 窪木拓男, 越野寿, 澤瀬隆, 角忠輝, 筒井睦

日本歯科医学教育学会総会・学術大会プログラム・抄録集 37回 76 - 76 2018年7月

The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin 査読

Khattab HM, Kubota S, Takigawa M, Kuboki T, Sebald W

J Bone Miner Metab. 128 ( 3 ) 181 - 196 2018年4月

A multi-centered epidemiological study evaluating the validity of the treatment difficulty indices developed by the Japan Prosthodontic Society. 査読

Takuo Kuboki, Tetsuo Ichikawa, Kazuyoshi Baba, Masanori Fujisawa, Hironobu Sato, Hideki Aita, Shigeto Koyama, Masayuki Hideshima, Yuji Sato, Hiroyuki Wake, Aya Kimura-Ono, Kan Nagao, Yorika Kodaira-Ueda, Katsushi Tamaki, Shinsuke Sadamori, Kazuhiro Tsuga, Yasuhiro Nishi, Takashi Sawase, Hisashi Koshino, Shin-Ichi Masumi, Kaoru Sakurai, Kanji Ishibashi, Takashi Ohyama, Yasumasa Akagawa, Toshihiro Hirai, Keiichi Sasaki, Kiyoshi Koyano, Hirofumi Yatani, Hideo Matsumura

Journal of prosthodontic research 62 ( 2 ) 162 - 170 2018年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier {BV}

PURPOSE: The Japan Prosthodontic Society developed a multi-axis assessment protocol to evaluate the complex variations in patients who need prosthodontic care, and to classify the level of treatment difficulty. A previous report found the protocol to be sufficiently reliable. The purpose of this multi-center cohort study was to evaluate the validity of this multi-axis assessment protocol. METHODS: The treatment difficulty was evaluated using the multi-axis assessment protocol before starting prosthodontic treatment. The time required for active prosthodontic treatment, medical resources such as treatment cost, and changes in the oral health-related QOL before and after treatment, were evaluated after treatment completion. The construct validity of this protocol was assessed by the correlation between the dentist's pre-operative subjective assessment of the treatment difficulty, and the level of difficulty determined by this protocol. The predictive validity was assessed estimating the correlations between a "comprehensive level of treatment difficulty" based on the four axes of this protocol and total treatment cost, total treatment time, and changes in the oral health-related QOL before and after treatment. RESULTS: The construct validity of this protocol was well documented except for psychological assessment. Regarding the predictive validity, the comprehensive level of treatment difficulty assessed before treatment was significantly correlated with the three surrogate endpoints known to be related to the treatment difficulty (total treatment cost, treatment time, and improvement in the oral health-related QOL). To further clarify the validity of the protocol according to patients' oral condition, a subgroup analysis by defects was performed. Analyses revealed that treatment difficulty assessment before treatment was significantly related to one or two surrogate endpoints in the fully edentulous patients and the partially edentulous patients. No significant relationship was observed in the patients with mixture of full/partial edentulism and the patients with teeth problems, possibly due to the small sample size in these groups. CONCLUSION: This study revealed that the multi-axis assessment protocol was sufficiently valid to predict the level of treatment difficulty in prosthodontic care in patients with fully edentulous defects and with partially edentulous defects.

DOI： 10.1016/j.jpor.2017.08.002

Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium. 国際誌

窪木拓男

Scientific Reports 8 ( 1 ) 2612 - 2612 2018年2月

Chondrocyte burst promotes space for mineral expansion. 査読国際誌

Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takako Hattori, Letycia Mary Iida, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto

Integrative biology : quantitative biosciences from nano to macro 10 ( 1 ) 57 - 66 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Royal Society of Chemistry ({RSC})

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.

DOI： 10.1039/c7ib00130d