Pseudoangiomatous Stromal Hyperplasia on Core Needle Biopsy Does Not Require Surgical Excision.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon, benign localized fibrotic lesion. Historically, PASH has been difficult to differentiate from angiosarcoma. This difficulty has led to recommendations of surgical excision.

Basic helix-loop-helix transcription factor Twist1 inhibits transactivator function of master chondrogenic regulator Sox9.

Canonical Wnt signaling strongly inhibits chondrogenesis. Previously, we identified Twist1 as a critical downstream mediator of Wnt in repression of chondrocyte differentiation. However, the mechanistic basis for the antichondrogenic activity of Twist1 has not heretofore been established.

N-cadherin adherens junctions mediate osteogenesis through PI3K signaling.

During endochondral ossification, the cartilage is surrounded by a layer of cells that constitute the perichondrium. Communication between osteoblasts in the perichondrium via N-cadherin adherens junctions is essential for endochondral bone growth. We observed that adherens junction molecule N-cadherin and its interacting partners p120, β-catenin and PTEN are expressed by cells present in the perichondrium.

A prospective randomised study of a rotary powered device (OnControl) for bone marrow aspiration and biopsy.

Introduction: Bone marrow aspiration and biopsy is an invasive procedure associated with morbidity and mortality risk. We compared a powered bone marrow aspiration and biopsy device to the traditional method by relatively assessing pain scores, procedure times, biopsy capture rates, quality of material retrieved, and safety and operator satisfaction.

Methods: Two large academic medical centres participated in this trial.

Conditional ablation of Pten in osteoprogenitors stimulates FGF signaling.

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a direct antagonist of phosphatidylinositol 3 kinase. Pten is a well recognized tumor suppressor and is one of the most commonly mutated genes in human malignancies. More recent studies of development and stem cell behavior have shown that PTEN regulates the growth and differentiation of progenitor cells.

Inhibition of autoregulated TGFbeta signaling simultaneously enhances proliferation and differentiation of kidney epithelium and promotes repair following renal ischemia.

We studied autocrine transforming growth factor (TGF)beta signaling in kidney epithelium. Cultured proximal tubule cells showed regulated signaling that was high during log-phase growth, low during contact-inhibited differentiation, and rapidly increased during regeneration of wounded epithelium. Autoregulation of signaling correlated with TGFbeta receptor and Smad7 levels, but not with active TGFbeta, which was barely measurable in the growth medium.

Direct interactions of Runx2 and canonical Wnt signaling induce FGF18.

Canonical Wnt signaling is clearly required for skeletal development and bone formation. However, the targets of Wnt signaling that convert this signal into bone are unclear. Identification of these targets will yield insight into normal bone physiology and suggest new therapeutics for treatment of bone disease.

The Wnt-inducible transcription factor Twist1 inhibits chondrogenesis.

Wnt signaling is essential for many developmental processes, including skeletogenesis. To investigate the effects of Wnt signaling during skeletogenesis we studied the effects of Wnt on cultured chondrocytic cells and differentiating limb-bud mesenchyme. We showed that Wnt3a strongly repressed chondrogenesis and chondrocyte gene expression.

Glycogen synthase kinase 3 controls endochondral bone development: contribution of fibroblast growth factor 18.

Glycogen synthase kinase 3 (GSK3) inhibits signaling pathways that are essential for bone development. To study the requirement for GSK activity during endochondral bone development, we inhibited GSK3 in cultured metatarsal bones with pharmacological antagonists. Interestingly, we find that inhibition of GSK3 strongly repressed chondrocyte and perichondrial osteoblast differentiation.

Regulation of sprouty expression by PLCgamma and calcium-dependent signals.

Sprouty, an essential antagonist of fibroblast growth factor receptor signaling, is induced following fibroblast growth factor receptor activation. The signaling pathways that induce sprouty have been incompletely characterized. However, studies show that MAP kinase signaling stimulates sprouty induction in various cell lines.

FGF18 represses noggin expression and is induced by calcineurin.

Fibroblast growth factors (FGFs) and bone morphogenetic proteins strongly regulate chondrogenesis and chondrocyte gene expression. The interactions of the signaling pathways initiated by these factors are central to the control of chondrocyte differentiation. Here we show that calcium-dependent signals induce expression of FGF18, an essential regulator of bone and cartilage differentiation.

Fibroblast growth factor receptor 3 gene: regulation by serum response factor.

We have previously identified a cis-acting sequence in the proximal promoter of the fibroblast growth factor receptor 3 (FGFR3) gene that strongly activates transcription in chondrocytic cells. Here we report that the transcriptional activity of this sequence (FRE3) requires serum response factor and its cognate recognition motif, serum response element. Although the FRE3 contains consensus sequence motifs for several transcription factors, the serum response element is paramount for the transcriptional activity of the FRE3.

Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation.

Mutations in fibroblast growth factor (FGF) receptor 3 lead to the human dwarfism syndrome achondroplasia. Using a limb culture system, we have analyzed the role of FGF signaling and its interaction with the Ihh/Pthlh and BMP pathways in regulating chondrocyte differentiation. In contrast to previous suggestions, we demonstrate that FGF signaling accelerates both the onset and the pace of hypertrophic differentiation.

Calcineurin and NFAT4 induce chondrogenesis.

Nuclear factor of activated T-cells (NFAT) and calcineurin are essential regulators of immune cell and mesenchymal cell differentiation. Here we show that elevated intracellular calcium induces chondrogenesis through a calcineurin/NFAT signaling axis that activates bone morphogenetic protein (BMP) expression. The calcium ionophore, ionomycin, induced chondrogenesis through activation of calcineurin.