掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

Abstract

The extracellular matrix of trabecular bone has a large surface exposed to the bone marrow and plays important roles such as hematopoietic stem cell niche formation and maintenance. In vitro reproduction of trabecular bone microenvironment would be valuable not only for developing a functional scaffold for bone marrow tissue engineering but also for understanding its biological functions. Herein, we analyzed and reproduced the initial stages of trabecular bone formation in mouse femur epiphysis. We identified that the trabecular bone formation progressed through the following steps: (i) partial rupture of hypertrophic chondrocytes; (ii) calcospherite formation on cell membrane nano fragments (CNFs) derived from the ruptured cells; and (iii) calcospherite growth and fusion to form the initial three-dimensional (3D) structure of trabecular bones. For reproducing the initial trabecular bone formation in vitro, we collected CNFs from cultured cells and used as nucleation sites for biomimetic calcospherite formation. Strikingly, almost the same 3D structure of the initial trabecular bone could be obtained in vitro by using additional CNFs as a binder to fuse biomimetic calcospherites.

DOI： 10.1093/rb/rbac088

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その他リンク： https://academic.oup.com/rb/article-pdf/doi/10.1093/rb/rbac088/48746035/rbac088.pdf

記述言語：日本語   出版者・発行元：埼玉県医学会  

類基底扁平上皮癌(Basaloid Squamous Cell Carcinoma:BSCC)は、扁平上皮癌の一亜型である。早期に再発・転移をきたすことから高悪性痛に分類されているが、口腔BSCCの発症は極めて稀であり、その病態像は不明瞭な点が多い。今回、2001年1月～2021年6月の約20年間に、本邦で報告された口腔BSCC 28例について検討し、国際的文献との比較を行った。本邦報告例は男性に多く、初診時年齢は60歳代が多かった。初発部位は舌と下顎歯肉に多かった。初診時臨床病期はStageI/IIが半数以上を占め、治療法は大部分が手術主体であった。一次治療後に原発巣再発を認めた症例は1例のみで、後発頸部リンパ節転移は2例(7.1%)と少なかった。一方、遠隔転移症例は5例(17.9%)にみられ、通常の口腔扁平上皮癌と比して遠隔転移率が高かった。遠隔転移を認めたほとんどの症例は一早期例で口腔BSCCの治療においては、早期例であっても集学的治療の選択を考慮すべきであると考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：岡山歯学会  

マウス軟骨前駆細胞ATDC5より生成した細胞ナノフラグメントを用いて石灰化物形成および三次元形成を行い、初期海綿骨形成をin vitroにて再現した。細胞ナノフラグメントを20mM塩化カルシウム水溶液と混和しpH9に調整し3日間反応し、生体内で観察された石灰化小球の生成に成功した。さらに生成した石灰化小球を3Dプリンターで作製した鋳型に充填・凍結乾燥して海綿骨様構造体を作製し走査型電子顕微鏡(SEM)で観察すると、発生初期海綿骨と同様の構造を認めた。また作製した海綿骨様構造体にマウス大腿骨骨髄由来細胞を播種して2週間培養した。その結果、SEMにて構造体表面および構造体内部に細胞の生着を認め細胞との高い親和性を確認できた。

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掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-β gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21.

DOI： 10.3390/ijms21207556

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Current stem cell-based techniques for bone-like tissue synthesis require at least two to three weeks. Therefore, novel techniques to promote rapid 3D bone-like tissue synthesis in vitro are still required. In this study, we explored the concept of using cell nanofragments as a substrate material to promote rapid bone formation in vitro. The methods for cell nanofragment fabrication were ultrasonication (30 s and 3 min), non-ionic detergent (triton 0.1% and 1%), or freeze-dried powder. The results showed that ultrasonication for 3 min allowed the fabrication of homogeneous nanofragments of less than 150 nm in length, which mineralized surprisingly in just one day, faster than the fragments obtained from all other methods. Further optimization of culture conditions indicated that a concentration of 10 mM or 100 mM of β-glycerophosphate enhanced, whereas fetal bovine serum (FBS) inhibited in a concentration-dependent manner, the mineralization of the cell nanofragments. Finally, a 3D collagen-cell nanofragment-mineral complex mimicking a bone-like structure was generated in just two days by combining the cell nanofragments in collagen gel. In conclusion, sonication for three min could be applied as a novel method to fabricate cell nanofragments of less than 150 nm in length, which can be used as a material for in vitro bone tissue engineering.

DOI： 10.3390/ijms21155327

PubMed

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記述言語：英語  

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse drug reaction represented by destruction and/or death of bone. Fibrous dysplasia (FD) is a rare bony disorder characterised by abnormal fibro-osseous tissue that has lowered resistance to infection. Effective treatments for BRONJ that follows FD are unclear. Here, we report that advanced BRONJ associated with FD was successfully treated by surgical resection. A 69-year-old woman, whose left maxillary bone showed a ground glass appearance on computed tomography (CT) images, was taking alendronate. At 1 year after teeth within the abnormal bone were extracted, exposed bone was observed in the extraction sites and CT images revealed separated sequestrums. Under the clinical diagnosis of Stage 2 BRONJ with FD, we performed not only sequestrectomy but also a partial resection of the FD. Thereafter, the healing was uneventful without recurrence. In conclusion, our case suggests that surgical resection is useful for advanced BRONJ associated with FD.

DOI： 10.1093/jscr/rjaa061

PubMed

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/jgf2.205

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