Resorption of bone collagen by multinucleated cells

Young donor rats of an isogenously related strain were injected with³H proline (1 Ci/g) and killed from 6 hours to 28 days later. The scapulae were removed, decalcified with EDTA and implanted subcutaneously into the backs of recipient rats. They were removed 14 days later with the surrounding tissue, sectioned, processed for autoradiography and stained with hematoxylin and eosin. In all cases there was a giant cell response round the bone. In bones removed from the donor animals 6 hours after proline injections, the label was on the edge of the appositional side of the bone and the giant cells did not remove it. By 28 days after proline administration when, due to apposition and resorption, the label was on the resorptive side of the bone, giant cells were seen removing the label, which however they did not ingest. It thus appears, as has been suggested in the literature, that recently formed bone collagen is removed with difficulty, but older collagen can be resorbed.This work was supported in part by Research Grant No. DE-1592 from the National Institute for Dental Research. National Institutes of Health.     

Anflutung und Verteilung von Alkohol bei oraler Resorption

Zusammenfassung Die geringere Alkohol-Konzentrationstoleranz während der Anflutungsphase kann auf eine stärkere Alkoholanflutung im Gehirn zurückgeführt werden. Die Ursache liegt in der gegenüber dem peripheren Venenblut überhöhten Alkoholkonzentration im arteriellen Blut und einem schnellen Konzentrationsausgleich zwischen arteriellem Blut und Hirngewebe. Die arterio-venöse Alkohol-Konzentrationsdifferenz nach Gabe von 0,8 g Alkohol (33 W/W% Lösung, 15 min Trinkzeit) wurde bei 5 Patienten einer Intensivstation bestimmt. Sie betrug maximal 0,27±0,20. Als maximale Alkoholkonzentration wurden im arteriellen Blut 0,94, im venösen 0,81 erreicht. Die Eliminationsrate ( 60) war mit 0,30±0,05 sehr hoch. Vergleichsweise wurde die Eliminationsrate ( 60-Wert) bei 5 Patienten während einer Halothan-Narkose bestimmt. Sie betrug 0,15±0,02 und lag damit im Normbereich. Auch Tierversuche an Ratten ergaben keine sicher verminderte Alkohol-Eliminationsrate unter Halothan. Eine mögliche geringe Verminderung des Äthanolabbaus durch kompetitive Hemmung der ADH-Aktivität durch das Halothan-Abbauprodukt Trifluoräthanol erscheint bei der Rückrechnung durch Anwendung eines 60-Wertes von 0,10 hinreichend berücksichtigt.Vortrag: 50. Jahrestagung der Deutschen Gesellschaft für Rechtsmedizin, Köln, 3.–7. 10. 1971.     

Different schedules of administration of (3 amino-1-hydroxypropylidene)-1, 1 bisphosphonate induce different changes in pig bone remodeling

Summary Intermittent administration of antiosteoclastic agents has been proposed in order to increase trabecular bone volume (TBV). We evaluated the effect of two different intermittent schedules of administration of (3 amino-1-hydroxypropylidene)-1, 1 bisphosphonate (AHPrBP) on pig bone remodeling for a period of 60 days. AHPrBP (1.6 μmol/kg/injection) was given subcutaneously daily (group A1), or 5 consecutive days out of 21 days (group A2), or 1 out of every fourth day (group A3). Compared to control animals, group A1 significantly increased trabecular bone volume (TBV) (+62%) with a marked decrease in bone resorption assessed by interstitial bone thickness. Bone formation assessed by mean wall thickness (MWT) was also decreased due to a decrease in the number and activity of osteoblasts. There was not a delay in the coupling mechanism as assessed by the reversal surfaces. The two groups receiving intermittent schedules had markedly different results. Group A2 had very similar changes to group A1 despite receiving four time less drug. Compared to group A1 and A2, group A3 had smaller decrease in resorption and higher bone formation rate with identical MWT. These differences between group A2 and A3 were associated with similar levels of parathyroid hormone and vitamin D metabolites. Different bone concentrations induced by the two different schedules of AHPrBP may explain the greater effect on bone resorption and osteoblast recruitment in group A2 and thus a milder effect of the AHPrBP administration once every fourth day.     

The Resorption of Vital and Devitalized Bone In Vitro: Significance for Bone Grafts

Several studies have suggested that devitalized bone is less satisfactory than live tissue for surgical grafting purposes because an initial resorption step, prior to new formation, is lacking. We have compared the osteoclastic resorption of cultured bone containing living osteocytes with that of similar bone in which the osteocytes were dead. In experiment I, transverse slices cut from freshly harvested adult rabbit femora were either placed in phosphate buffered saline (Set 1) or subjected to freezing and thawing (Set 2). In experiment II, a heated set (Set 3) was prepared in addition. All slices were cultured with osteoclasts for 24 hours, eight slices per set being seeded with bone cells in experiment I and three per set in experiment II. The areas and volumes of resorption pits formed during the culture period were measured using reflection confocal microscopy. In both experiments, the mean values for the areas of the pits were smaller in the bone containing live osteocytes (P < 0.03, Mann Whitney test), and in experiment II the volumes of the pits in Set 1 were smaller than those in Set 3 (P < 0.0001, Mann Whitney test). However, in neither experiment was there a significant difference between the Sets in the volume:area ratios (mean depths) of the pits. The findings show that devitalized bone is resorbed by osteoclasts at least as readily as bone containing vital osteocytes in vitro, and indicate that if grafted devitalized bone resorbs less well in vivo it is not because the bone tissue is intrinsically resistant to osteoclastic resorption. Received: 25 November 1997 / Accepted: 24 June 1998     

Cell proliferation and apoptosis of thyroid follicular cells are involved in the involution of experimental non-tumoral hyperplastic goiter

 It is unknown whether cells in the midportion of Meckel’s cartilage undergo transformation into other kinds of cell or whether resorption of cells occurs during development. Therefore, the midportion of Meckel’s cartilage from the mouse and the rat was subdivided into anterior and posterior portions. The ultimate fates of these tissues were analyzed with a focus on resorption-related cells, death of chondrocytes by apoptosis, and transformation of the chondrocytes themselves. Cellular and extracellular features of mouse Meckel’s cartilage were observed after von Kossa’s staining and staining for acid phosphatase (APase) activity, as well as by light and electron microscopy. To identify resorbing cells, immunostaining specific for macrophages and staining for tartrate-resistant acid phosphatase (TRAP) were performed. The DNA nick end-labeling (TUNEL) method was used for the detection of death of chondrocytes by apoptosis. The replacement of the extracellular matrix of rat Meckel’s cartilage was examined with double immunofluorescence staining for type I and type II collagens. When the anterior midportion from embryonic mice on day 18 was examined after von Kossa’s staining, it was clear that the extracellular matrix had already calcified and vascularization had been initiated that reflected the calcified matrix. TRAP staining and immunostaining for macrophages revealed two types of osteoclast and macrophages that were involved in resorption of the matrix. In the posterior midportion, no vascular invasion was evident, and chondrocytes were transformed directly into fibroblastic cells by phenotypic conversion. In such cells we found reaction products specific for APase activity, suggestive of the intracellular degradation of fine collagenous fibrils. Double immunofluorescence staining showed that cartilage-specific type II collagen was replaced by type I collagen with the phenotypic transformation to fibroblastic cells. There were no significant changes in the number of TUNEL-positive apoptotic cells from day 17 of gestation to day 6 after parturition. Death of chondrocytes by apoptosis was not, therefore, involved directly in the disappearance of Meckel’s cartilage. These results in the posterior midportion served as an instance of phenotypic switches in differentiated cells from chondrocytes to fibroblast-like cells. The present study indicates that there is a difference between the ultimate fate of cells in the posterior part and that of cells in the anterior part in the midportion of Meckel’s cartilage in the mouse and rat. Accepted: 8 January 1998     

颅面部贴附植骨的实验研究

目的 探讨颅面骨表面贴附植骨吸收的内在机理。方法 实验用30只成年雄性新西兰白兔,随机均分成两组,采用自体颅有及肋骨块贴附移植于颅面骨表面。术后12周及24周分别取材,行大体观察,体积测量,组织学观察及电镜观察。结果 颅骨吸收少,移植骨皮质部在吸收改建过程中变化较大,颅骨或肋嘣骨胶原纤维的数量及排列24周比12周多而有规律。12周时,颅骨骨胶原纤维的数量及排列优于肋骨,而24周时,两种骨无差别,移植骨即使已经成活,内部构造还未完全成熟,移植骨体积进一步减少。结论 颅面部贴附植骨膜内化骨优于软骨内化骨,移植骨的皮质部是导致两种骨吸收不同的关键部位,移植骨的体积维持也与应力有关。     

BM210955对破骨细胞骨吸收的抑制作用

细胞水平研究国产双磷酸盐药物－ＢＭ２１０９５５的骨吸收抑制作用。由１日龄ＳＤ大鼠四肢长骨分离破骨细胞（ＯＣ）并接种于牛皮质骨薄切片上,在不同浓度ＢＭ２１０９５５作用下培养,定时取骨片作ＴＲＡＰ免疫组化染色,计数阳性多核细胞后,经超声去除细胞后作甲苯胺蓝染色,光镜下作吸收陷窝计数,数据以ｘ±ｓ表示,并与对照比较作ｔ检验。结果显示：①ＢＭ２１０９５５能降低体外培养ＯＣ的数目,１０－８ｍｏｌ／Ｌ组的ＴＲＡＰ阳性多核细胞较对照组减少７３％,差异具有非常显著性,Ｐ＜０．０１。②ＢＭ２１０９５５抑制ＯＣ的陷窝形成能力,１０－１０、１０－８ｍｏｌ／Ｌ组的抑制率分别为７６．３２％和８７．９９％,均与对照有明显差异,Ｐ＜０．０１。③上述结果与剂量有关,剂量越高,抑制效应越明显