Distinct osteogenic mechanisms of bones of distinct origins

Mammalian bones have three distinct origins (paraxial mesoderm, lateral plate mesoderm, and neural crest) and undergo two different modes of formation (intra-membranous and endochondral). Bones derived from the paraxial mesoderm and lateral plate mesoderm mainly form through the endochondral process. During this process, hypertrophic chondrocytes play a vital role in inducing both osteogenesis and angiogenesis. One of the essential osteogenic factors secreted from hypertrophic chondrocytes is Indian hedgehog (Ihh). In contrast, bones derived from the neural crest mainly form through the intramembranous pro-cess and do not require Ihh. Thus, depending on their origin, bones have distinct signaling properties, which need to be considered in the research and application of bone biology.Presented at the 18th Annual Research Meeting of the Japanese Orthopaedic Association, Kitakyushu, Japan, October 17, 2003     

神经化组织工程骨构建的初步观察

目的评估两种组织工程骨体内神经化重建方法的成骨效果,研究神经化与成骨的相互关系。方法26只新西兰大白兔,其中24只随机分成四组:组织工程骨组(A组),感觉神经束植入组(B组),运动神经束植入组(C组),血管束植入组(D组);另2只为空白对照组。每只动物均制备左侧股骨长1.5cm的段缺性骨与骨膜缺损,钢板固定后骨缺损处分别植入用四种方法制备的组织工程骨。植入的神经分别是隐神经和股神经肌支。术后4、8、12周摄股骨正位X线片,用放射影像学评分和X线阻射影分析比较骨缺损修复情况。结果在组织工程骨中植入感觉神经束后,比单纯组织工程骨和运动神经束植入的修复效果均有明显提高,而在组织工程骨中植入运动神经束与单纯组织工程骨修复骨缺损的效果相比较无明显差异,感觉神经束植入与血管束植入的成骨效果比较无明显差异,血管束植入组的成骨效果优于其它两组。结论利用感觉神经束植入的方法可以提高组织工程骨的成骨作用,而植入运动神经束却无此作用。     

四种可溶性载体对骨形态发生蛋白在小鼠体内诱导成骨活性的影响

以四种可溶性物质作为牛骨形态发生蛋白（ｂＢＭＰ）的载体，通过实验观察哪种物质是ｂＢＭＰ的有效缓释载体。将聚乙烯吡咯烷酮（ＰＶＰ）、葡聚糖、羟乙基淀粉（ＨＥＳ）、甘露醇分别与等量ｂＢＭＰ复合后，注射入小鼠股部肌肉，观察组织学成骨及测定标本内钙含量。结果，ｂＢＭＰ／ＰＶＰ有良好成骨，吸收较快，未见炎症及排斥反应，其混悬液较稳定，具有良好的适针性及可注射性，ｂＢＭＰ／甘露醇只有很低成骨率。其余各组未见成骨。ＰＶＰ对ｂＢＭＰ具有满意助溶、助悬及缓释载体作用，对ｂＢＭＰ活性无损害，生物相容性好。     

中面部牵引成骨术后眶周结构三维位置变化的评估

目的 观察中面部牵引成骨技术对眼眶周围软、硬组织结构的三维空间位置变化的影响.方法 回顾性分析2003年9月至2006年6月接受Le Fort III型截骨+中面部牵引成骨术的8例Crouzon综合征患者CT数据,平均年龄11.9岁,实施影像三维重建后,采用眶耳平面(术前)作为测量的基准平面,分别选择眶上点、眶下点、眶内缘点、眶外缘点、眼球前点、眼球后点,以及上、下、内、外四直肌与眼球的附着点作为评估标志,以双侧耳门上点连线作为颅底宽度基准,记录各个主要标志点至耳门上点连线的矢状距(y轴向)、垂直距(z轴向)以及眼球前点、眼球后点的水平间距(x轴向)变化,行配对t检验,并与健康对照组比较.结果 牵引成骨术前后眼球前点的y轴向及z轴向位置并没有显著性变化,但x轴向间距变化为-3.40 mm;眶下点移动在y轴向平均12.24 mm,z轴向平均4.25 mm;眶内缘点移动在y轴向平均10.11 mm,z轴向平均2.80 mm;眶外缘点移动在y轴向平均9.86 mm,z轴向平均2.31mm;下直肌支点移动,y轴向平均3.63mm,z轴向平均2.98mm.其余各标记点未见有临床意义的位移变化.结论 以Le Fort III型截骨为主的面中部牵引成骨技术,可以使Crouzon综合征患者的术后眼眶内、外、下侧壁均出现明显的前、下方移位,而患者的眼球没有显著性的矢状向位置变化,仅呈现轻度的内移、下降和前上方旋转.     

Über die Anwendung von Wachstumshormon bei Osteoporose

Zusammenfassung Über einen Zeitraum von 8 bis 12 Monaten wurden 1 Patient mit primärer und 2 Patienten mit sekundärer Osteoporose bei Osteogenesis imperfecta mit hochgereinigtem Wachstumshormon aus menschlichen Hypophysen behandelt. Aus den Ergebnissen der laborchemischen, knochenhistologischen und kinetischen Untersuchungen mit⁴⁷Calcium vor und nach der Therapie ließ sich kein positiver Effekt auf die Knochenerkrankung ermitteln. Dies steht im Gegensatz zu tierexperimentellen Untersuchungen an ausgewachsenen Hunden, bei denen es bereits 3 Monate nach Beginn der Applikation von Wachstumshormon zu einer Positivierung der Knochenbilanz gekommen war.     

Homology-mediated recombination between type I collagen gene exons results in an internal tandem duplication and lethal osteogenesis imperfecta

It has been proposed that the structure of the exons that encode the triple helical domain of the fibrillar collagen genes arose by repeated tandem duplication of an ancestral unit exon. Because these exons encode a repeat motif [(Gly-X-Y)_n], sequence homology between exons may have driven the recombinational process. We have characterized a tandem duplication mutation within a COL1A1 allele of type I collagen from an infant with the lethal form of osteogenesis imperfecta. The structure of the mutation is consistent with the occurrence of an unequal crossover within a 15 base pair region of sequence identity between exons 14 and 17 of the COL1A1 gene. The recombination produced a new 81 base pair 17/14 hybrid exon and complete duplication of exons 15 and 16. The sequence implies duplication of 60 amino acid residues within the triple helical domain with preservation of the Gly-X-Y repeat. These data suggest that a recombinational mechanism that explains the hypothetical evolutionary process is active in cells, but the lethal effect of this mutation raises questions about the role of these events in creating new structures for polymeric proteins. © 1993 Wiley-Liss, Inc.     

Kappa Delta Award paper. Osteoregulatory nature of mechanical stimuli: function as a determinant for adaptive remodeling in bone

The capacity for functional adaptation within the skeleton was studied using the functionally isolated turkey ulna preparation. The results of this study would suggest that adaptive bone remodeling is extremely sensitive to alterations in both the magnitude and distribution of the strain generated within the bone tissue. At present, it appears that a loading regime can only influence bone remodeling when it is dynamic in nature. The full osteogenic potential of its influence is then achieved after only an extremely short exposure to this stimulus. The potency of the stimulus appears to be proportional to the magnitude of the strain engendered. As strain levels that are acceptable in one location induce adaptive remodeling in others, it would appear that each region of each bone is "genetically programmed" to accept a particular amount and pattern of intermittent strain as "normal." Deviation from this "optimal strain environment" will stimulate changes in the bone's remodeling balance, resulting in adaptive increases or decreases in its mass.     

Osteosarcoma occurring in osteogenesis imperfecta

We describe a case history of a 24-year-old male with osteogenesis imperfecta (OI) who developed osteosarcoma of the left thigh. High-dose ifosfamide therapy caused marked tumor regression of multiple lung metastases. Immunohistochemically, the tumor cells were diffusely positive for the p53 protein. Mutation of the p53 gene was not detected by direct genomic sequencing of exons 4–8. The radiographic characteristics, including irregularly distributed osteolytic lesions and cortical discontinuity, should not be confused with hyperplastic callus formation, a benign process. A biopsy is critical to establish the differential diagnosis between osteosarcoma and common hyperplastic callus formation in OI; however, it must be applied with great care.     

Repair of cartilaginous fractures during chick limb development.

The embryonic chick wing has been used extensively in experimental analyses of the mechanisms involved in limb development. This study employs the embryonic wing in an examination of the possible origin of congenital pseudoarthrosis, a poorly understood limb disorder. To this end, chick radii were fractured in the middiaphysis prior to the onset of osteogenesis (6.5-7 days of incubation). The subsequent development of the fractured elements was examined using both whole mount preparations and histology. Callus cartilage did not form around any of the fractures. Nonetheless, the majority (29 of 33 specimens) of fractures united during primary osteogenesis (within 24-36 h of the operation), with bone formation occurring both across the fracture site and also over the cut ends of the cartilage. In addition, bones that exhibited a configuration similar to that described as giving rise to a type II congenital pseudoarthrotic condition were obtained. Typically, these bones showed an "hourglass" constriction midshaft and anterior bowing. These results suggest that the embryonic chick limb may serve as a useful experimental model system for the investigation of this congenital limb disorder.     

The effect of electric fields on osteoporosis of disuse

Summary An experiment originally done by McElhaney et al. was repeated to obtain additional information about the effects of electrical fields on osteoporosis of disuse. The right femurs of 35 male rats were immobilized in plaster casts. Sixteen rats were treated with transcutaneous electrical fields of 30 Hz and 100 V/cm for periods of 2 or 8 h a day. While the right femurs of the untreated rats were found to be atrophic with respect to the opposite limb, in the treated rats the immobilized femur was made larger than the opposite bone. Longer daily treatments exaggerated this effect. The tumors found in the previous study were not seen in our experiments. Other similarities and differences in the 2 studies are discussed.