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PubMed2007

Genetic network and pathway analysis of differentially expressed proteins during critical cellular events in fracture repair.

Bone repair consists of inflammation, intramembranous ossification, chondrogenesis, endochondral ossification, and remodeling. To better understand the translational regulation of these distinct but interrelated cellular events, we used the second generation of BD Clontechtrade mark Antibody Microarray to dissect and functionally characterize proteins differentially expressed between intact and fractured rat femur at each of these cellular events. Genetic network analysis showed that proteins differentially expressed within a given cellular event tend to be physically or functionally correlated. Seventeen such interacting networks were established over five cellular events that were most frequently associated with cell cycle, cell death, cell-to-cell signaling and interaction, and cell growth and proliferation. Eighteen molecular pathways were significantly enriched during the bone repair process, of which ERK/MAPK, NF-kB, PDGF, and T-cell receptor signaling pathways were significant during three or more cellular events. The analyses revealed dynamic temporal expression patterns and cellular-event-specific functions. The inflammation event on Day 1 was characteristic of the cell cycle-related molecular changes. The relative quiet stage of intramembranous ossification on Day 4 and the molecularly most active stage of chondrogenesis on Day 7 were featured by coordinated cell death and cell-proliferation signals. Endochondral ossification on Day 14 experienced a clear transition from the molecular/cellular function to the physiological system development/function. The osteoclast-mediated remodeling on Day 28 was highlighted by the integrin signaling pathway. The distinct changes in protein expression during these cellular events provide a molecular basis for developing cellular event-targeted therapeutic strategy to accelerate bone healing.

Animals↗
PubMed1983

Ossification of thoracic ligamenta flava.

Although ligamentum flavum ossification (LFO) often occurs in normal persons, there are no reports of its detection on lateral chest radiographs made during screening examinations. Review of 1,744 consecutive lateral chest radiographs identified LFO in 6.2% of males and 4.8% of females. LFO occurred mainly at the intervertebral segments from T9-T10 through T12-L1. Most prevalent was the hook-shaped LFO, protruding inferiorly from the inferior facets into the projections of the intervertebral foramina. Though LFO can cause severe neurologic symptoms, none of the affected persons in this study reported such symptoms. LFO was first visualized radiographically when the subjects were 20-40 years old, and it may be a physiologic condition. The LFO in these cases existed independent of thoracic posterior longitudinal ligament ossification, diffuse idiopathic skeletal hyperostosis, and degenerative osteoarthritis.

Adult↗
PubMed2004

Asymmetric closure of ischiopubic synchondrosis in pediatric patients: correlation with foot dominance.

OBJECTIVE: The enlarged ischiopubic synchondrosis is a well-known anatomic structure; however, little is known about its physiology. In early childhood, enlargement of this synchondrosis occurs bilaterally, whereas before complete ossification, it is frequently found unilaterally. In most children, the unilateral enlarged ischiopubic synchondrosis is observed in the left hemipelvis, a finding that was hitherto unexplained. During common athletic activities, increased ground reaction forces are exerted on the weight-bearing nondominant limb, which in up to 87% of the general population is the left leg. The asymmetric exertion of these forces may explain the distinct closure sequence of this temporary joint. The purpose of this study was to correlate unilateral enlarged ischiopubic synchondrosis with foot dominance. MATERIALS AND METHODS: The study cohort comprised 32 children who had undergone unenhanced radiography, CT, or MRI for reasons other than bone disorders and who presented with enlarged ischiopubic synchondroses. In these children, the distribution of enlarged ischiopubic synchondrosis and foot dominance were evaluated either retrospectively (n = 11) or prospectively (n = 21). RESULTS: In this cohort, 78% of patients were right-footed and 22% were left-footed. Nine of the 32 children presented with unilateral enlarged ischiopubic synchondrosis (left, seven [78%] of nine; right, two [22%] of nine). All children with enlarged left ischiopubic synchondrosis were right-footed, and all children with enlarged right ischiopubic synchondrosis were left-footed. CONCLUSION: Unilateral enlarged ischiopubic synchondrosis is closely correlated with foot dominance. The asymmetric ossification pattern of the ischiopubic synchondrosis indicates delayed ossification of this anatomic structure due to asymmetrically applied mechanical forces to the nondominant limb.

Adolescent↗
PubMed1983

Radiology of postnatal skeletal development. VIII. Distal tibia and fibula.

Initially the distal tibial physis is a relatively transverse structure. As the epiphysis matures, undulations develop within the physis and lappet formation occurs peripherally. Within the first two years a significant physeal undulation develops anteriorly above the medial malleolus. This undulation must not be misinterpreted as premature epiphyseodesis following distal tibial fracture. Secondary ossification in the distal tibia begins centrally and initially expands to fill the area over the tibial plafond. At the lateral side of the tibial epiphysis the ossification center may be wedge-shaped. The medial margin adjacent to the medial malleolus is often irregular and may show small peripheral foci of ossification. By seven to eight years, the secondary center extends into the medial malleolus, with complete distal extension often not occurring until adolescence (although usually complete by ten to eleven years). The malleolar tip may exhibit an accessory ossification center. However, this center also may be a traumatic avulsion in the symptomatic patient. Physiologic epiphyseodesis begins over the medial malleolus and subsequently extends laterally. This pattern of closure appears to predispose to fracture of the lateral portion of the distal tibial epiphysis (fracture of Tillaux), as well as to triplane fractures. The articular surface curves onto the lateral side of the distal tibia to form an articulation with the lateral malleolus (distal tibiofibular joint). A similar extension occurs along the medial side of the fibula. These surfaces extend proximally as a recess to the level of the distal tibial physis, at which point the syndesmosis begins. The initially transverse distal fibular physis becomes a convoluted structure, with extensive peripheral lappet formation. Within these regions of physeal overlap there may be small areas of accessory ossification (both medially and laterally) that should not be misinterpreted as fractures. This overlapping also minimizes specific physeal separation and displacement (especially when compared to the incidence of distal tibial physeal injuries). Stress views may be necessary to show such an undisplaced fracture. The fibular physis normally is level with the tibial articular surface or distal extent of the tibial ossification center, especially after the second year of life (however, it may be more proximal in infants). As in the medial malleolus, there may be accessory ossification at the tip of the fibula. While this usually is a normal variant of secondary ossification, occasionally it also may result from trauma. Extensive porosity of the distal fibular metaphysis predisposes to buckling or torus injuries that may have severe, multiangular deformation.

Adolescent↗
PubMed2001

The inhibitory effects of colchicine on cell proliferation and mineralisation in culture.

Colchicine is often used in the treatment of diseases such as familial Mediterranean fever (FMF) and gout. We have previously reported that patients with FMF who had colchicine on a daily basis and who had a total hip arthroplasty showed no heterotopic ossification after surgery. The mechanism by which colchicine causes this clinical phenomenon has never been elucidated. We therefore evaluated the effect of various concentrations of colchicine on cell proliferation and mineralisation in tissue culture, using rat and human cells with and without osteogenic potential. Cell proliferation was assessed by direct cell counts and uptake of (3H)thymidine, and mineralisation by measuring the amount of staining by Alizarin Red. Our findings indicate that concentrations of colchicine of up to 3 ng/ml did not affect cell proliferation but inhibition was observed at 10 to 30 ng/ml. Mineralisation decreased to almost 50%, which was the maximum inhibition observed, at concentrations of colchicine of 2.5 ng/ml. These results indicate that colchicine at low concentrations, of up to 3 ng/ml, has the capacity to inhibit selectively bone-like cell mineralisation in culture, without affecting cell proliferation. Further clinical and laboratory studies are necessary to evaluate the effects of colchicine on biological processes involving the proliferation of osteoblasts and tissue mineralisation in vivo, such as the healing of fractures, the formation of heterotopic bone and neoplastic bone growth.

Animals↗
PubMed1994

Growth and skeletal development in the dog in relation to nutrition; a review.

Longitudinal growth of the appendicular skeleton in the growth plates and the adjacent metaphyseal area includes chondrocyte differentiation, proliferation, maturation, and hypertrophy in the physis and bone (re-) modelling in the metaphysis. The rate and extent of longitudinal growth are regulated by interactions between biomechanical factors and endogenous growth regulators, i.e., systemic endocrine factors, and local para or autocrine factors, that act on the growth plate chondrocytes. The most important endogenous regulators of growth and skeletal development are growth hormone (GH) and insulin-like growth factors (IGFs), and calciotropic hormones, i.e., parathyroid hormone (PTH), vitamin D (vitD), and calcitonin (CT). The biochemistry, synthesis, secretion, target organs, and effects of these endogenous factors are reviewed, and the calcium homeostatic mechanisms, dietary intake, bone turnover, and calcium excretion are discussed. Energy, protein, and calcium are nutritional factors of great importance to (skeletal) growth. The effects of low and high dietary intake of these nutrients are discussed, especially with reference to longitudinal growth and disturbances in endochondral ossification.

Animal Nutritional Physiological Phenomena↗
PubMed1999

Strain-related bone remodeling in distraction osteogenesis of the mandible.

Distraction osteogenesis has become a mainstay in craniofacial surgery. However, there are several unresolved problems concerning the biology of bone regeneration. We investigated the biomechanical effects of mandibular lengthening in 32 rabbits on a cellular and histologic level. The mandible was subjected to a corticotomy, held in a neutral position for 4 days, and then lengthened at various strain rates and frequencies for 10 days. Radiographic, histologic, and electron microscopic examinations showed a strain-related bone regeneration. Application of physiologic strain rates (2000 microstrains or 0.2 percent) led to a bridging of the artificial fracture exhibiting woven ossification, whereas at 20,000 microstrains trabecular bone formation was demonstrated. In contrast, hyperphysiologic strain magnitudes (200,000 microstrains and 300,000 microstrains) showed a fibrous tissue formation. Multiple strain applications (10 cycles/day versus 1 cycle/day) increased the width of the distraction gap without changing the stage of bone regeneration. The gradual distraction of bone in physiologic magnitudes at higher frequencies seems to be desirable for a bony differentiation and may help to improve clinical applications.

Animals↗