0000000000237255
AUTHOR
Michael Amling
showing 6 related works from this author
Wnt1 Promotes Cementum and Alveolar Bone Growth in a Time-Dependent Manner
2021
The WNT/β-catenin signaling pathway plays a central role in the biology of the periodontium, yet the function of specific extracellular WNT ligands remains poorly understood. By using a Wnt1-inducible transgenic mouse model targeting Col1a1-expressing alveolar osteoblasts, odontoblasts, and cementoblasts, we demonstrate that the WNT ligand WNT1 is a strong promoter of cementum and alveolar bone formation in vivo. We induced Wnt1 expression for 1, 3, or 9 wk in Wnt1Tg mice and analyzed them at the age of 6 wk and 12 wk. Micro–computed tomography (CT) analyses of the mandibles revealed a 1.8-fold increased bone volume after 1 and 3 wk of Wnt1 expression and a 3-fold increased bone volume aft…
Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand.
2018
Wnt signaling is important for proper embryonic development, shaping cell fate and migration, stem cell renewal, and organ and tissue formation. Here, Luther et al. investigated the role of Wnt1 in osteoporosis. Patients with early-onset osteoporosis and with WNT1 mutations had low bone turnover and high fracture rates, and loss of Wnt1 activity caused fracture and osteoporosis in mice. Inducing Wnt1 in bone-forming cells increased bone mass in aged mice, and this process did not require Lrp5, a co-receptor involved in Wnt signaling. This study identifies Wnt1 as an anabolic (bone building) factor and suggests that it might be a therapeutic target for osteoporosis.WNT1 mutations in humans a…
Ibandronate: a review of its vertebral and nonvertebral antifracture efficacy.
2009
After the Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE) study had demonstrated the strong vertebral and nonvertebral antifracture efficacy of daily and intermittent oral ibandronate, the Monthly Oral Ibandronate In Ladies (MOBILE) study gave evidence for an increased efficacy on the bone mineral density (BMD) of higher intermittent oral ibandronate doses (150 mg monthly) compared with 2.5 mg daily. The BONE study also observed nonvertebral antifracture efficacy in patients with a high risk for fractures (mean femoral neck T score of −3.0 or less). A recently published meta-analysis assessing the nonvertebral antifracture efficacy corresponding to the …
Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3.
2014
Many neurodegenerative disorders present with sensory loss. In the group of hereditary sensory and autonomic neuropathies loss of nociception is one of the disease hallmarks. To determine underlying factors of sensory neurodegeneration we performed whole-exome sequencing in affected individuals with the disorder. In a family with sensory neuropathy with loss of pain perception and destruction of the pedal skeleton we report a missense mutation in a highly conserved amino acid residue of atlastin GTPase 3 (ATL3), an endoplasmic reticulum-shaping GTPase. The same mutation (p.Tyr192Cys) was identified in a second family with similar clinical outcome by screening a large cohort of 115 patients …
Epidermal IL-17A leads to bone loss through inhibition of osteoblast differentiation
2012
The AP-1 transcription factor family is a central regulator of skin and bone homeostasis. We have previously shown that specific deletion of JunB/AP-1 in epidermis (JunBmice) results in skin inflammation,myeloproliferative disease, lupus-like disease and osteopenia. While upregulation of serum IL-6 and G-CSF are observed in this model, genetic deletion of these cytokines does not rescue osteopenia in JunB mice. Thus, we carried out a screen for other cytokines that are regulated by the loss of JunB in the epidermis. We have identified IL-17A as a cytokine expressed in JunB epidermis in vivo, and hypothesize that IL-17A leads to osteopenia in JunBmice. To test this,we carried out osteoblast …
Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts
2016
Item does not contain fulltext Inflammation has important roles in tissue regeneration, autoimmunity, and cancer. Different inflammatory stimuli can lead to bone loss by mechanisms that are not well understood. We show that skin inflammation induces bone loss in mice and humans. In psoriasis, one of the prototypic IL-17A-mediated inflammatory human skin diseases, low bone formation and bone loss correlated with increased serum IL-17A levels. Similarly, in two mouse models with chronic IL-17A-mediated skin inflammation,K14-IL17A(ind)andJunB(Deltaep), strong inhibition of bone formation was observed, different from classical inflammatory bone loss where osteoclast activation leads to bone deg…