Bone Abstracts

Aim: Wnt/β-catenin pathway promotes cartilage breakdown in osteoarthritis. We have previously shown that sclerostin preserves chondrocyte maintenance in vitro by reducing chondrocyte catabolism through the inhibition of Wnt/β-catenin pathway. However, sclerostin restores partially the expression of the anabolic genes. We therefore investigated the effect of sclerostin in the activation of Wnt non canonical pathways mediated by Ca2+/CaMKII, JNK, an...

Background: Cartilage matrix breakdown in osteoarthritis (OA) is due to mechanical stress and inflammation leading to increased metalloproteinases (MMPs) production. Currently, IL1β is thought to have a major role in this process. IL1β is synthesized as an inactive precursor, which is cleaved into the secreted active form. This maturation process mainly occurs in the inflammasome complex. Inflammasome is constituted by initiators (including NALP3) and adaptor molecul...

Background and aims: Cirrhosis and chronic pancreatitis (CP) are accompanied by inflammation and malnutrition. Both conditions may affect bone metabolism negatively and facilitate bone fractures. The objective of this study was to evaluate the risk of fractures among patients with CP or cirrhosis and the impact of fat malabsorption on fracture risk among patients with CP.Methods: Using the Danish National Patient Register, we did a retrospective cohort s...

Sclerostin, a product of osteocytes, is known to inhibit Wnt signaling by binding the LRP5/6 receptor.We investigated the effects of a mutated mouse sclerostin protein (muScl, R118A/R144A) with potential sclerostin antagonistic activity. In vitro, muScl fully competed with wild type sclerostin for binding to LRP6, whereas its IC50 for Wnt3a activity was 4× higher than sclerostin (i.e. 600 nM). Moreover, serum osteocalcin increased in mice a...

Background: A 5-month-old girl was referred to our unit after a systemic screening for hip dislocation by X-rays revealed bilateral femoral bowing. She was the first child of healthy non-consanguineous parents, and her family history was unremarkable. Her parents had a normal physical examination, and normal laboratory findings. At presentation, her height was 64.0 cm (Z-score: 0.0) with a regular height velocity. Weight was 7.4 kg (Z-score: 1.0). On physical...

Objective: To assess the relationship between thyrotoxicosis and osteoporotic fractures in men and women.Design: Register-based cohort study in patients with a TSH measurement in the region of Funen 1996–2010. All determinations were done in the same lab serving all hospitals and GP practices. Persons with raised TSH or a history of thyroid/pituitary disease were not included.Results: The study population consisted of 222 138 ...

Purpose: Sclerostin, a Wnt inhibitor produced by osteocytes that regulate bone remodelling, might be involved in cartilage metabolism. Therefore, we assessed the effect of sclerostin in osteoarthritis using SOST-deficient mice.Methods: SOST-KO and wild type (WT) mice underwent partial meniscectomie (Mnx). Mice were sacrificed at 4, 6 or 9 weeks after Mnx to analyze i) bone volume (BV/TV) at the femoral condyle, ii) osteophyte volume (microCT), iii) carti...

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Objective: Cartilage loss and subchondral bone changes are hallmarks of osteoarthritis (OA). The Wnt family is involved in the regulation of bone and cartilage. We have shown that the Wnt/β-catenin pathway is activated in bone during OA, but the effect of its inhibition in bone in cartilage remodeling is unknown. We here investigated the impact of the bone-specific inhibition of Wnt during the development of OA.Methods: Partial meniscectomy (Mnx) wa...

It is still unknown where from osteoblasts are recruited during remodeling of adult human cancellous bone. Still, it is often suggested that they originate from perivascular osteoprogenitors in the bone marrow (BM). Here we propose also the existence of a layer of osteoprogenitors at the periphery of the BM. This proposal is based on electron and light microscopy of the bone surface and of the neighboring BM in human iliac crest biopsies, where we quantified cell densities, ce...