Activation of Hedgehog signaling in mesenchymal stem cells induces cartilage and bone tumor formation via Wnt/ β-Catenin

Indian Hedgehog (IHH) signaling, a key regulator of skeletal development, is highly activated in cartilage and bone tumors. Yet deletion of Ptch1, encoding an inhibitor of IHH receptor Smoothened (SMO), in chondrocyte or osteoblasts does not cause tumorigenesis. Here, we show thatPtch1deletion in mice Prrx1+ mesenchymal stem/stromal cells (MSCs) promotes MSC proliferation and osteogenic and chondrogenic differentiation but inhibits adipogenic differentiation. Moreover,Ptch1 deletion led to development of osteoarthritis-like phenotypes, exostoses, enchondroma, and osteosarcoma in Smo-Gli1/2-dependent manners. The cartilage and bone tumors are originated from Prrx1+ lineage cells and express low levels of osteoblast and chondrocyte markers, respectively. Mechanistically,Ptch1 deletion increases the expression of Wnt5a/6 and leads to enhanced b-Catenin activation. Inhibiting Wnt/b-Catenin pathway suppresses development of skeletal anomalies including enchondroma and osteosarcoma. These findings suggest that cartilage/bone tumors arise from their early progenitor cells and identify the Wnt/b-Catenin pathway as a pharmacological target for cartilage/bone neoplasms.
Source: eLife - Category: Biomedical Science Tags: Cancer Biology Cell Biology Source Type: research

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Publication date: Available online 25 January 2020Source: Journal of OrthopaedicsAuthor(s): Yoshinori Ishii, Hideo Noguchi, Junko Sato, Hana Ishii, Ryo Ishii, Shin-ichi ToyabeAbstractBackgroundProlonged operative time has frequently been implicated as a risk factor for various complications after total knee arthroplasty (TKA). We aimed to determine whether preoperative factors such as sex, age, body mass index (BMI), prosthetic design, tibiofemoral angle (TFA), range of motion, coronal laxity, Hospital for Special Surgery score and periarticular bone mineral density (BMD) affect operative time.MethodsWe evaluated 164 patie...
Source: Journal of Orthopaedics - Category: Orthopaedics Source Type: research
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Source: Ophthalmic Epidemiology - Category: Opthalmology Authors: Source Type: research
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Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
Source: BMJ Comments - Category: General Medicine Source Type: forums
Source: BMJ Comments - Category: General Medicine Source Type: forums
Extracellular vesicles (EVs) are heterogeneous nanosized vesicles that are constitutively released by virtually all types of cells. They have been isolated in almost all body fluids. EVs cargo consists of various molecules (nucleic acids, proteins, lipids, and metabolites), that can be found on EVs surface and/or in their lumen. EVs structure confer stability and allow the transfer of their cargo to specific cell types over a distance. EVs play a critical role in intercellular communication in physiological and pathological settings. The broadening of knowledge on EVs improved our comprehension of cancer biology as far as ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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