Bone Formation

Bronner, Felix; Farach‐Carson, Mary C.

doi:10.1007/978-1-4471-3777-1

Cited by 44 publications

(78 citation statements)

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“…For each section, the calcified cartilage/subchondral bone junction was used as the upper limit of each field, which was readily determined using both Safranin-O and H&E stained serial sections. The depth of measurement was limited to the upper limit down to 500 µm, consistent to methods previously described 117,[130][131][132] . All statistical differences between parameters of samples with meniscectomy and with sham-operation were compared using a student's t-test at p<0.05.…”

Section: Bone Histomorphometrymentioning

confidence: 99%

Modulating hedgehog signaling can attenuate the severity of osteoarthritis

Lin

Seeto

Bartoszko

et al. 2009

Nat Med

299

340

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Osteoarthritis is associated with the irreversible degeneration of articular cartilage. Notably, in this condition, articular cartilage chondrocytes undergo phenotypic and gene expression changes that are reminiscent of their end-stage differentiation in the growth plate during skeletal development. Hedgehog (Hh) signaling regulates normal chondrocyte growth and differentiation; however, the role of Hh signaling in chondrocytes in osteoarthritis is unknown. Here I examined human osteoarthritic samples and mice in which osteoarthritis was surgically induced and find that Hh signaling is activated in osteoarthritis. Using several genetically modified mice, I found that higher levels of Hh signaling in chondrocytes cause a more severe osteoarthritic phenotype. Furthermore, Ishow in mice and in human cartilage explants that pharmacological or genetic inhibition of Hh signaling reduces the severity of osteoarthritis and that runtrelated transcription factor-2 (Runx2) potentially mediates this process by regulating a disintegrin and metalloproteinase with thrombospondin type 1 motif-5 (Adamts5) expression. Together, these findings raise the possibility that Hh blockade can be used as a therapeutic approach to inhibit articular cartilage degeneration.iii ACKNOWLEDGEMENTS

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Section: Bone Histomorphometrymentioning

confidence: 99%

Modulating hedgehog signaling can attenuate the severity of osteoarthritis

Lin

Seeto

Bartoszko

et al. 2009

Nat Med

299

340

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“…Developmental modularity might allow different signaling pathways to regulate the rates of growth independently within each module at specific times, allowing for precise regulation of bone shape. However, even though many genes are involved in mandibular formation (Bronner et al, 2010), no functional evidence exists that demonstrates how specific molecular activities can impose such regulation.…”

Section: Introductionmentioning

confidence: 99%

Hedgehog-dependent proliferation drives modular growth during morphogenesis of a dermal bone

2012

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SUMMARYIn the developing skeleton, dermal bone morphogenesis includes the balanced proliferation, recruitment and differentiation of osteoblast precursors, yet how bones acquire unique morphologies is unknown. We show that Hedgehog (Hh) signaling mediates bone shaping during early morphogenesis of the opercle (Op), a well characterized dermal bone of the zebrafish craniofacial skeleton. ihha is specifically expressed in a local population of active osteoblasts along the principal growing edge of the bone. Mutational studies show that Hh signaling by this osteoblast population is both necessary and sufficient for full recruitment of pre-osteoblasts into the signaling population. Loss of ihha function results in locally reduced proliferation of pre-osteoblasts and consequent reductions in recruitment into the osteoblast pool, reduced bone edge length and reduced outgrowth. Conversely, hyperactive Hh signaling in ptch1 mutants causes opposite defects in proliferation and growth. Time-lapse microscopy of early Op morphogenesis using transgenically labeled osteoblasts demonstrates that ihha-dependent bone development is not only region specific, but also begins exactly at the onset of a second phase of morphogenesis, when the early bone begins to reshape into a more complex form. These features strongly support a hypothesis that dermal bone development is modular, with different gene sets functioning at specific times and locations to pattern growth. The Hh-dependent module is not limited to this second phase of bone growth: during later larval development, the Op is fused along the dysmorphic edge to adjacent dermal bones. Hence, patterning within a module may include adjacent regions of functionally related bones and might require that signaling pathways function over an extended period of development.

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“…1 mM sodium pyruvate, 100 nM dexamethansone, 50 M ascorbic acid 2-phosphate, and 10 mM ␤-glycerophosphate for 5 to 7 days (26). We characterized the obtained cells on the basis of expression of osteocalcin, osteopontin, SPARC (secreted protein acidic and rich in cysteine), and alkaline phosphatase; the ability to build extracellular matrix (collagen I); and their mineralization as mature osteoblasts (5,28,40). The cells were detached with Accutase for passage or seeding.…”

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confidence: 99%

Influence on Mitochondria and Cytotoxicity of Different Antibiotics Administered in High Concentrations on Primary Human Osteoblasts and Cell Lines

Duewelhenke

Krut

Eysel

2007

Antimicrob Agents Chemother

177

138

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Osteomyelitis, osteitis, spondylodiscitis, septic arthritis, and prosthetic joint infections still represent the worst complications of orthopedic surgery and traumatology. Successful treatment requires, besides surgical débridement, long-term systemic and high-concentration local antibiotic therapy, with possible local antibiotic concentrations of 100 g/ml and more. In this study, we investigated the effect of 20 different antibiotics on primary human osteoblasts (PHO), the osteosarcoma cell line MG63, and the epithelial cell line HeLa. High concentrations of fluoroquinolones, macrolides, clindamycin, chloramphenicol, rifampin, tetracycline, and linezolid during 48 h of incubation inhibited proliferation and metabolic activity, whereas aminoglycosides and inhibitors of bacterial cell wall synthesis did not. Twenty percent inhibitory concentrations for proliferation of PHO were determined as 20 to 40 g/ml for macrolides, clindamycin, and rifampin, 60 to 80 g/ml for chloramphenicol, tetracylin, and fluoroquinolones, and 240 g/ml for linezolid. The proliferation of the cell lines was always less inhibited. We established the measurement of extracellular lactate concentration as an indicator of glycolysis using inhibitors of the respiratory chain (antimycin A, rotenone, and sodium azide) and glycolysis (iodoacetic acid) as reference compounds, whereas inhibition of the respiratory chain increased and inhibition of glycolysis decreased lactate production. The measurement of extracellular lactate concentration revealed that fluoroquinolones, macrolides, clindamycin, rifampin, tetracycline, and especially chloramphenicol and linezolid impaired mitochondrial energetics in high concentrations. This explains partly the observed inhibition of metabolic activity and proliferation in our experiments. Because of differences in the energy metabolism, PHO provided a more sensitive model for orthopedic antibiotic usage than stable cell lines.

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Bone Formation

Cited by 44 publications

References 0 publications

Modulating hedgehog signaling can attenuate the severity of osteoarthritis

Modulating hedgehog signaling can attenuate the severity of osteoarthritis

Hedgehog-dependent proliferation drives modular growth during morphogenesis of a dermal bone

Influence on Mitochondria and Cytotoxicity of Different Antibiotics Administered in High Concentrations on Primary Human Osteoblasts and Cell Lines

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