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PubMed2005

Effect of reduced oxygen tension on chondrogenesis and osteogenesis in adipose-derived mesenchymal cells.

Recent studies have demonstrated that adipose-derived mesenchymal cells (AMCs) offer great promise for cell-based therapies because of their ability to differentiate toward bone, cartilage, and fat. Given that cartilage is an avascular tissue and that mesenchymal cells experience hypoxia during prechondrogenic condensation in endochondral ossification, the goal of this study was to understand the influence of oxygen tension on AMC differentiation into bone and cartilage. In vitro chondrogenesis was induced using a three-dimensional micromass culture model supplemented with TGF-beta1. Collagen II production and extracellular matrix proteoglycans were assessed with immunohistochemistry and Alcian blue staining, respectively. Strikingly, micromasses differentiated in reduced oxygen tension (2% O(2)) showed markedly decreased chondrogenesis. Osteogenesis was induced using osteogenic medium supplemented with retinoic acid or vitamin D and was assessed with alkaline phosphatase activity and mineralization. AMCs differentiated in both 21 and 2% O(2) environments. However, osteogenesis was severely diminished in a low-oxygen environment. These data demonstrated that hypoxia strongly inhibits in vitro chondrogenesis and osteogenesis in AMCs.

Adipose Tissue↗
PubMed2006

Understanding the information needs of general practitioners managing a rare genetic disorder (osteogenesis imperfecta).

BACKGROUND: Lack of adequate knowledge is a common problem in medicine, but is a particular problem in a rapidly advancing field like genetics. This study uses the example of a rare genetic disorder (osteogenesis imperfecta) to understand the information needs of primary care physicians (GPs). OBJECTIVES: To determine whether a knowledge gap is recognised, how GPs currently attempt to overcome it, and what features of an information resource are preferred by GPs. METHODS: GPs of children affected by osteogenesis imperfecta in and around Greater London were interviewed, using both questionnaire-based semi-structured interview and a qualitatively analysed open-ended discussion. Consultations in both primary and tertiary care settings over a 5-year period were compared. RESULTS: Problems due to osteogenesis imperfecta were presented to GPs in about one third of consultations with these patients. GPs reported finding such patients difficult to manage due to lack of knowledge. Knowledge from tertiary sources, which was authoritative, accessible and relevant, was preferred, particularly when reasoning was explained. Primary literature and clinical guidelines were not favoured. CONCLUSIONS: Empirical evidence supports and elaborates theoretical models for provision of clinically useful information. A model for improved information services using authoritative web-based information linked to electronic patient records is suggested.

Adolescent↗
PubMed1992

Fibroblast growth factor: effects on osteogenesis and chondrogenesis in the chick embryo.

In vivo effects of fibroblast growth factor (FGF) on osteogenesis were evaluated in the chick embryo. Autoradiographic studies of 3H-proline labeling over bone matrix indicated that 24 h after treatment on day 11, FGF stimulated osteogenic cell proliferation, while inhibiting the production of bone matrix collagen. However, 4 days after multiple doses of FGF, the large pool of newly formed osteogenic and chondrogenic cells expressed their function with the increased formation of matrix. The data provide in vivo evidence of the effects of exogenous FGF on osteogenesis and also point to a possible role for FGF both in embryonic osteogenesis and in fracture repair.

Animals↗
PubMedDate not supplied

Stapes surgery in patients with osteogenesis imperfecta.

Osteogenesis imperfecta is not in itself a contraindication to stapedectomy. Thirty stapedectomies were performed on 24 patients with osteogenesis imperfecta. Thin ossicles, crural fractures, and thick, mushy, granular footplates predominate in this condition. Deficient, short crura that did not contact the footplate were noted in three patients; this is possibly a new clinical observation. Three times in this small series the endosteum was so thick that it was possible to fenestrate the soft, granular, mush-like footplate without invading the vestibule. Extreme caution in handling the incus is necessary. Conductive hearing loss can be relieved through stapedectomy in patients with osteogenesis imperfecta with about the same level of predictability as in those with otosclerosis.

Adult↗
PubMed1995

Cellular patterns of insulin-like growth factor system gene expression in murine chondrogenesis and osteogenesis.

In situ hybridization histochemistry was used to map cellular patterns of gene expression for the insulin-like growth factor (IGF) system in developing murine skeleton from embryonic day 15 (E15) through postnatal day 25 (P25). IGF-I receptor and IGF-II receptor messenger RNAs (mRNAs) are both selectively concentrated in developing chondrocytes and osteoblasts. IGF-II and IGF-binding protein-5 and -6(IGFBP-5 and -6) mRNAs are abundant in mesenchymal condensations and chondroblasts on E15. Chondrocyte IGF-II mRNA levels remain high, but IGFBP-5 and -6 mRNAs decline significantly as cartilage matures. Low levels of IGFBP-6 mRNA are detected in postnatal chondrocytes up to at least P25, but IGFBP-5 mRNA is no longer detected in chondrocytes after E18. IGF-I and IGFBP-2, -3, and -4 mRNAs are detected in surrounding mesenchymal tissue, but are not detected in mesenchymal condensations or chondrocytes at any stage of development. IGFBP-3 mRNA is localized in sprouting capillaries invading the perichondrium and periosteum throughout development. IGF-I, IGF-II, and IGFBP-2, -4, -5, and -6 mRNAs are detected in osteoblasts localized in zones of endochondral ossification from E18 to at least P25. IGFBP-1 mRNA is not detected in cartilage or bone cells at any stage of development. These data confirm the recent report by Shinar et al. that IGF-II, but not IGF-I, mRNA is detected in rat chondrocytes in vivo and show that this pattern also applies to the mouse. The present study demonstrates, for the first time, the cell-specific patterns of IGF-I and -II receptor and IGFBP-2 to -6 gene expression during the processes of chondro- and osteogenesis in vivo. Interestingly, IGF-II, both IGF receptors, and IGFBP-5 and -6 are simultaneously coexpressed in chondrocyte precursors early in skeletal development, suggesting functional interactions between these specific factors in chondrogenesis. Both IGFs, both IGF receptors, and IGFBP-2, -4, -5, and -6 are all expressed in osteoblasts, providing evidence for potential local interactions between these IGF system components in osteogenesis. Thus, 9 of 10 known components of the IGF system demonstrate dynamic cell-specific patterns of gene expression during chondro- and osteogenesis, supporting the view that the IGF system has a complex and integral role within the developing skeleton.

Animals↗
PubMed1977

Effect of long-term calcitonin therapy on the clinical course of osteogenesis imperfecta.

10 children with osteogenesis imperfecta, 4 with "tarda" and 6 with "congenita" varieties of the disease, were treated with salmon calcitonin (SCT) for intervals ranging from 14 to 35 months. Responses to SCT therapy in patients with osteogenesis imperfecta tarda were characterized by an apparent decreased fracture incidence in three, a fall in either alkaline or acid phosphatase, and a rate of increase in forearm bone mass which was greater than that observed in an untreated "tarda" population. The chemical response SCT therapy varied in children with osteogenesis imperfecta congenita, only one demonstrating a decrease in both acid phosphatase and urinary hydroxyproline. Three others responded with a rise in acid phosphatase, two of whom also demonstrated a fall in urinary hydroxyproline; in two other "congenita" patients urinary hydroxyproline was actually higher after SCT treatment and acid phosphatase relatively unchanged. Alkaline phosphatase was normal in all "congenita" patients before and following the SCT treatment interval. These varied biochemical responses were associated with temporary increments in bone mass early in the treatment course, although in bone mass early in the treatment course, although one "congenita" patient with the largest calciuric response to SCT and an increase in hydroxyproline excretion demonstrated progressive increments in skeletal mineral content during a 14-month treatment interval. In both "tarda" and "congenita" subjects, parathyroid hormone was unchanged by chronic SCT treatment; SCT-antibodies were detectable although biological responsivity to SCT persisted.

Acid Phosphatase↗
PubMed1981

Osteogenesis in bone grafts after short-term storage and topical antibiotic treatment. An experimental study in rats.

It has been shown in experimental animals that the living cells in a bone autograft can make an important contribution to osteogenesis. However, some common clinical techniques, such as the topical use of antibiotic powders on grafts or on the graft bed, are likely to damage or kill the cells. In this experimental study in rats, bone isografts dusted with chloramphenicol or methicillin powder or with Polybactrin spray before subcutaneous implantation produced little or no new bone over a period of two weeks whereas untreated, control grafts showed abundant osteogenesis, as did grafts pretreated with solutions of antibiotics. The effect of short-term storage of the grafts for 3 to 24 hours in air, saline or culture medium before implantation was also examined. Grafts stored in culture medium generally did as well as, or better than, fresh control grafts whereas immersion in saline inhibited osteogenesis. The importance of these results for clinical bone grafting is discussed.

Animals↗
PubMed1985

Costovertebral anomalies in osteogenesis imperfecta.

Study of 16 patients with Type III osteogenesis imperfecta showed marked elongation of the pedicles of the vertebrae in all cases, a deformity which was not seen in other types of the disease. Posterior rib angulation was also noted in Type III disease. These features have proved useful in suggesting the diagnosis of osteogenesis imperfecta even before long bones have fractured and in categorizing patients with osteogenesis imperfecta into the correct type for prognostic purposes.

Biomechanical Phenomena↗
PubMed2002

Application of locked intramedullary nails in the treatment of complications after distraction osteogenesis.

Distraction osteogenesis (callotasis) has been widely used in patients with limb-length inequality or massive bone defects. This procedure, however, may be associated with a high incidence of physical and psychosocial complications. Callotasis telescoping on a locked intramedullary nail has been used to shorten the period of external fixation. Little attention has been given to the use of locked intramedullary nails in the treatment of complications after callotasis. Between 1990 and 1999, we used locked intramedullary nailing in 27 patients for the treatment of complications after distraction osteogenesis. There were 17 men and ten women with a mean age of 33.2 years (16 to 66). The nail was inserted at a mean of 3.4 weeks (0 to 15) after removal of the external fixator. Simultaneous autogenous bone grafting and soft-tissue reconstruction were also undertaken in seven and two patients, respectively. There was consolidation of the callus or docking site in all patients at a mean of 6.4 months (2 to 14) after surgery. The mean shortening of the callus was 0.7 cm (0 to 2.5). Two patients had infection at the site of a distal screw which resolved after removal of the nail. In 17 patients the nail was removed at a mean of 26 months after its insertion. Locked intramedullary nails are useful in treating complications after distraction osteogenesis in skeletally mature patients. The risk of infection should be borne in mind.

Adolescent↗
PubMed2002

Osteosarcoma around the knee. Intraepiphyseal excision and biological reconstruction with distraction osteogenesis.

In 11 patients juxta-articular osteosarcoma around the knee was treated by intraepiphyseal excision of the tumour and reconstruction of the bone defect by distraction osteogenesis. Preoperative and postoperative chemotherapy was given to eight patients with high-grade tumours. The articular cartilage of the epiphysis and a maximum of healthy soft tissues were preserved. Distraction osteogenesis was then carried out. The mean gain in length was 9.7 cm. Full function of the limb was preserved in all except one patient, with a mean follow-up of 53.8 months. Treatment of juxta-articular osteosarcomas around the knee with joint preservation and biological reconstruction using distraction osteogenesis can give excellent functional results.

Adolescent↗
PubMed2000

The expression of metalloproteinase-2, -9, and -14 and of tissue inhibitors-1 and -2 is developmentally modulated during osteogenesis in vitro, the mature osteoblastic phenotype expressing metalloproteinase-14.

During osteogenesis, in vitro, of tibial-derived rat osteoblasts (ROB) and derived clones, changes occur in the interactions of mature osteoblasts with the endogenous extracellular matrix (ECM) and these culminate in the formation of tridimensional nodules, which become sites of mineral deposition. We investigated if these changes might be mediated by remodeling of ECM, and we focused our study on the neutral metalloproteinases (MMPs), known agents of matrix remodeling, and on their tissue inhibitors (TIMPs). We report that during in vitro differentiation, osteoblasts express the secreted MMP-2 and -9 and the membrane gelatinase MMP-14. These, along with the tissue inhibitors TIMP-1 and -2, are developmentally regulated according to the maturation stage of osteoblasts. Their levels change in a similar association with osteoblast phenotypic maturation in different populations of ROB, which take different times to complete osteogenesis in vitro. MMP-14 expression coincides in both cell populations with the mature osteoblastic phenotype and is localized in the cells forming nodules. MMP-2 and -9 are expressed diffusely in the osteoblast population. Developmentally associated changes in the activation of MMP-2 are detected, associated in their timing with the expression of MMP-14 in both populations of ROB, and MMP-14 activates pro-MMP-2 in vitro. Expression of messenger RNAs (mRNAs) for the three MMPs increases up to the time of nodule formation. At this stage, TIMP-1 mRNA levels are lowest. TIMP-2 mRNA decreases throughout osteogenesis. In situ hybridization in 7-day-old rat tibias shows the strongest expression of MMP-14 among osteogenic cells, in lining osteoblasts on the newly formed trabeculae under the growth plate, and on the endosteal surface of cortical bone. Our data support the concept that the developmentally regulated expression of MMP-14 triggers localized proteolysis within the osteogenic population, concomitant in vitro to nodule formation.

Animals↗
PubMed2002

Systemic regulation of distraction osteogenesis: a cascade of biochemical factors.

This study investigates the systemic biochemical regulation of fracture healing in distraction osteogenesis compared with rigid osteotomy in a prospective in vivo study in humans. To further clarify the influence of mechanical strain on the regulation of bone formation, bone growth factors (insulin-like growth factor [IGF] I, IGF binding protein [IGFBP] 3, transforming growth factor [TGF] beta1, and basic FGF [bFGF]), bone matrix degrading enzymes (matrix-metalloproteinases [MMPs] 1, 2, and 3), human growth hormone (hGH), and bone formation markers (ALP, bone-specific ALP [BAP], and osteocalcin [OC]) have been analyzed in serum samples from 10 patients in each group pre- and postoperatively. In the distraction group, a significant postoperative increase in MMP-1, bFGF, ALP, and BAP could be observed during the lengthening and the consolidation period when compared with the baseline levels. Osteotomy fracture healing without the traction stimulus failed to induce a corresponding increase in these factors. In addition, comparison of both groups revealed a significantly higher increase in TGF-beta1, IGF-I, IGFBP-3, and hGH in the lengthening group during the distraction period, indicating key regulatory functions in mechanotransduction. The time courses of changes in MMP-1, bone growth factors (TGF-beta1 and bFGF), and hGH, respectively, correlated significantly during the lengthening phase, indicating common regulatory pathways for these factors in distraction osteogenesis. Significant correlation between the osteoblastic marker BAP, TGF-beta1, and bFGF suggests strain-activated osteoblastic cells as a major source of systemically increased bone growth factors during callus distraction. The systemic increase in bFGF and MMP-1 might reflect an increased local stimulation of angiogenesis during distraction osteogenesis.

Adult↗
PubMed2007

An immunohistochemical analysis of the temporal and spatial expression of growth factors FGF 1, 2 and 18, IGF 1 and 2, and TGFbeta1 during distraction osteogenesis.

Distraction osteogenesis (DO) is a well established surgical technique that generates new bone by gradual distraction of two bony segments. In this study, we investigated the temporal and spatial profile of FGF 1, 2 and 18, IGF 1 and 2, and TGFbeta1 during distraction osteogenesis using immunohistochemistry. An osteotomy was performed on the right tibia of 13 white male New Zealand rabbits. After a delay of 7 days, distraction was started at a rate of 0.25 mm/12 hrs for 3 weeks which was followed by a 3 week period of consolidation. Immunohistochemical analysis was performed on a weekly interval to determine the expression of the growth factors. Staining of all growth factors was apparent at various levels in the centre and callus region in fibroblasts and chondrocyte cells. FGF2 however, showed continued high expression in osteoblasts. Within two weeks after the end of distraction all growth factors showed a reduction in expression except for FGF18 which maintained high levels of expression (up to 100% staining) throughout the distraction and consolidation phases. The study suggests that in comparison to the other investigated growth factors, FGF18 may play in important role throughout the entire process of distraction osteogenesis.

Animals↗
PubMed1995

Comparison of the values of basic fibroblast growth factor determined by an immunoassay in the sera of patients with traumatic brain injury and enhanced osteogenesis and the effects of the same sera on the fibroblast growth in vitro.

In patients with severe traumatic brain injury, the early healing of fractures is accompanied by hypertrophic callus formation or heterotopic ossifications, which might even result in ankylosis of the affected joints. Analysis of the sera of patients with traumatic brain injury revealed post-traumatic dynamic changes of basic fibroblast growth factor immunoreactivity, similar to those observed during fracture healing associated with enhanced osteogenesis. The aim of this study was to determine whether such changes in basic fibroblast growth factor concentrations could be related to the phenomenon of enhanced osteogenesis. Basic fibroblast growth factor immunoreactivity was determined (using an IEMA kit) in the sera of patients with traumatic brain injury and bone fractures (n = 8) and in the sera of patients with either traumatic brain injury alone (n = 10) or bone fractures alone (n = 7), and the effects of these sera on L929 fibroblast growth were analysed in vitro. The results did not prove a causative relationship between the changes of basic fibroblast growth factor immunoreactivity and in vitro growth promoting effects of the sera. However, it is apparent that, in addition to changes in the growth-promoting activity and basic fibroblast growth factor concentration of serum, other as yet unknown post-traumatic changes can cause enhanced osteogenesis.

Adolescent↗
PubMed2003

Vertical alveolar distraction osteogenesis with complications in a reconstructed mandible.

We report here a case of vertical alveolar distraction osteogenesis with many complications that required further surgical interventions. A 54-year-old man underwent mandibular resection followed by iliac bone grafting as the result of large mandibular odontogenic keratocyst. Eleven months later, alveolar vertical distraction osteogenesis was applied to the patient for prosthetic rehabilitation. Fracture of the basal bone occurred in the consolidation period, and the fracture was fixed by the titanium miniplate system. Radiographic examination after completion of distraction osteogenesis confirmed a radiolucent area in half of the distracted area between the basal bone and the transport segment, and when the distractor was removed the radiolucent area was filled with fibrous granulation tissue. The granulation tissue was removed and endosteal implants were inserted together with a bone graft. Ultimately, all implants were osseointegrated, and adequate esthetics and function of the implant-supported prosthesis were achieved.

Alveolar Bone Loss↗
PubMed1999

Mandibular lengthening by distraction osteogenesis in children--a one-year follow-up study.

OBJECTIVE: The present study was undertaken to document whether mandibular length could be increased by distraction osteogenesis in children and what happens to the mandibular position 1 year after the distraction. METHODS: Five patients with hemifacial microsomia (four unilateral, one bilateral) had distraction osteogenesis performed to lengthen the mandible. All patients had cephalometric and panoramic radiographs obtained before and 3, 6, and 12 months after the distraction osteogenesis. RESULTS: The total mandibular length (Co-Gn) on the affected side was increased by 11.2 mm after the distraction and remained stable during a 1-year observation period. However, the increased mandibular length tended to move the chin downward (8 mm) more than forward (2 mm) during the same period. CONCLUSIONS: Distraction osteogensis can be used to lengthen the hypoplastic mandible. However, most of the increased mandibular length moved the chin downward more than forward.

Activator Appliances↗
PubMed2003

Rigid external distraction osteogenesis for a patient with maxillary hypoplasia and oligodontia.

OBJECTIVE: In this report, the orthodontic treatment combined with rigid external distraction osteogenesis in a 5.5-year-old girl with midfacial hypoplasia and oligodontia is described. PATIENT: The child presented with a reduced maxilla, protruding lower lip, skeletal Class III jaw relationship with a low mandibular plane angle, a short and flattened nose, anterior crossbite, and aplasia of 16 permanent teeth. The patient was treated with rigid external maxillary distraction osteogenesis, maxillary protraction headgear, and Class III elastics. Following treatment, the maxilla was displaced in a forward direction with new bone formation at the tuberosities and the mandible rotated backward in relation to the anterior cranial base. The anterior crossbite was corrected, and the skeletal jaw relationship changed from a Class III to a Class I skeletal pattern. The soft tissue facial profile showed that the nasal projection had been increased, the nasolabial angle increased, and the lower lip protrusion was reduced. Postoperative treatment results were acceptable. CONCLUSION: This report documents that early maxillary advancement with rigid external osteogenesis offers a promising treatment alternative for a very young patient with maxillary hypoplasia and oligodontia.

Anodontia↗
PubMed2006

Expression of neurotrophins and their receptors tropomyosin-related kinases (Trk) under tension-stress during distraction osteogenesis.

The localization and expression of neurotrophins and their receptors during distraction osteogenesis was investigated in 72 male rat femurs (11 weeks old) to further clarify the concurrence of cellular and molecular events of new bone formation. After osteotomy, a 7-day lag phase was followed by distraction at the rate of 0.25 mm/12 h for 21 days (distraction phase), and a 7-day consolidation phase. The localization of neurotrophins (NGF, BDNF and NT-3) and their receptors tropomyosinrelated kinases (TRKA, TRKB and TRKC) by immunostaining showed positive staining in bone forming cells in each stage, although the presence and staining intensity varied by cell type and phase. The expressions of NGF, BDNF and NT-3 by real-time polymerase chain reaction (real-time PCR) showed that the peak of the mRNA expression of NGF occurred 10 days after distraction. NT-3 increased during bone extension, but decreased when distraction stopped. In contrast, BDNF continued to increase gradually throughout the distraction and consolidation phases. These findings suggest that neurotrophins and their receptors may play different roles in endochondral and intramembranous ossification in distraction osteogenesis. The tension stress caused by distraction may stimulate the expression of neurotrophins and their receptors, and promote osteogenesis.

Animals↗