scholarly journals Increased expression of osteopontin in subchondral bone promotes bone turnover and remodeling, and accelerates the progression of OA in a mouse model

Aging ◽  
2022 ◽  
Author(s):  
Chuangxin Lin ◽  
Zhong Chen ◽  
Dong Guo ◽  
Laixi Zhou ◽  
Sipeng Lin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Turnover ◽  
Subchondral Bone

The ClC-5 Knockout Mouse Model of Dent's Disease Has Renal Hypercalciuria and Increased Bone Turnover

2003 ◽  
Vol 18 (4) ◽  
pp. 615-623 ◽  
Author(s):  
Ian V Silva ◽  
Valeriu Cebotaru ◽  
Hua Wang ◽  
Xi-Tao Wang ◽  
Sha Sha Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Turnover ◽  
Knockout Mouse ◽  
Dent’S Disease ◽  
Knockout Mouse Model ◽  
Dent's Disease ◽  
Renal Hypercalciuria

scholarly journals Early Changes of Articular Cartilage and Subchondral Bone in The DMM Mouse Model of Osteoarthritis

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Hang Fang ◽  
Lisi Huang ◽  
Ian Welch ◽  
Chris Norley ◽  
David W. Holdsworth ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mouse Model ◽  
Subchondral Bone

scholarly journals Zoledronic Acid Reverses Acute Bone Impairment in a Mouse Model for Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 222-222 ◽  
Author(s):  
Luca Dalle Carbonare ◽  
Alessandro Matte ◽  
Maria Teresa Valenti ◽  
Angela Siciliano ◽  
Arianna Cristellon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zoledronic Acid ◽  
Sickle Cell Disease ◽  
Mouse Model ◽  
Bone Turnover ◽  
Osteogenic Differentiation ◽  
Molecular Analysis ◽  
Bone Structure ◽  
Bone Fragility ◽  
Cell Disease

Abstract Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by the synthesis of pathological hemoglobin S (HbS). Up to now, limited studies in SCD patients have proposed a bone loss related to recurrent acute vaso-occlusive events (VOCs). Here, we designed a study in a humanized mouse model for SCD to evaluate (i) bone structure turnover and micro-architecture by histomorphometric approach; (ii) osteoblastic differentiation by RT-PCR analysis of bone runx2, sparc and alp gene expression. We used humanized healthy control (Hbatm1(HBA)Tow Hbbtm3(HBG1,HBB)Tow) and SCD (Hbatm1(HBA)Tow Hbbtm2(HBG1,HBB*)Tow) mice. Mice were divided into different groups as detailed in the enclosed flow-chart. In steady state, we first evaluated bone-marrow erythropoiesis by FACS analysis based on CD44-TER119 strategy. No signs of ineffective erythropoiesis were detectable in SCD mice compared to controls. Bone analysis was performed by histomorphometric approach after double labelling with demeclocycline followed by calcein to evaluate the dynamic parameters of bone turnover and analyzed by a specific software (bone3.1, Explora Nova, Larochelle, France). The histomorphometric bone analysis revealed (i) reduced bone volume with associated decreased trabecular number and increased trabecular separation; (ii) increased bone-turnover measured as bone formation rate (BFR) and activation frequency (AcF); (iii) decreased number of nodes (NdN) and node termini ratio; (iv) increased marrow star volume (MSV) and fractal dimension (D) compared to healthy mice. The bone molecular analysis revealed a significant down-regulation of runx2, sparc and alp gene expression in SCD mice compared to healthy ones. These data indicate a severe osteoporosis with bone fragility associated with alteration of osteogenic differentiation in SCD mice. Zoledronic acid (Zol) is the most powerful available bisphosphonate used to reduce bone turnover and bone fragility. Since VOCs are life-threatening complication of SCD and mainly involved skeletal system, requiring multidiscliplinary approach, we exposed SCD and control mice to hypoxia/reoxygenation (H/R) stress to mimic acute VOCs (see flow-chart). Mice were exposed to hypoxia (8% oxygen, 10 hours) followed by reoxygenation (21% oxygen) for either 18 hours to carry out molecular analysis or 10 days to carry out histomorphometric analysis. In H/R exposed vehicle treated SCD mice, we found (i) a significant increase in AcF (bone turnover), without differences in bone structure and microarchitecture compared to SCD mice under normoxia; (ii) a further reduction in osteogenic differentiation molecular markers. Zol (100 μg/ Kg in a single ip injection) was administrated either 7 days before (Zol-pre) or immediately after (Zol-post) H/R stress. In SCD mice, both Zol-pre and Zol-post significantly prevented the H/R induced increased bone turnover, while no differences were detectable in bone structure and microarchitecture compared to vehicle treated H/R SCD mice. The molecular analysis showed that Zol increased the osteogenic related gene expression, indicating a positive induction of osteogenic differentiation. Our data suggest that murine SCD is characterized by a significant bone impairment related to the unbalance between osteoblastic/osteoclastic activity in favor of osteoclastic one in presence of a down-regulation of osteogenic differentiation. In SCD, Zol plays a pivotal role decreasing osteoclastic activity and promoting osteogenic differentiation, representing a powerful new therapeutic strategy to limit bone disease in SCD. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Subchondral bone turnover, but not bone volume, is increased in early stage osteoarthritic lesions in the human hip joint

2015 ◽  
Vol 23 (12) ◽  
pp. 2167-2173 ◽  
Author(s):  
R. Klose-Jensen ◽  
L.B. Hartlev ◽  
L.W.T. Boel ◽  
M.B. Laursen ◽  
K. Stengaard-Pedersen ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Subchondral Bone ◽  
Hip Joint ◽  
Early Stage ◽  
Bone Volume

scholarly journals Roles for B[a]P and FICZ in subchondral bone metabolism and experimental temporomandibular joint osteoarthritis via the AhR/Cyp1a1 signaling axis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuri Yoshikawa ◽  
Takashi Izawa ◽  
Yusaku Hamada ◽  
Hiroko Takenaga ◽  
Ziyi Wang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Mouse Model ◽  
Bone Metabolism ◽  
Temporomandibular Joint ◽  
Subchondral Bone ◽  
Dependent Manner ◽  
Bone Homeostasis ◽  
Wild Type ◽  
Temporomandibular Joint Osteoarthritis ◽  
Signaling Axis

AbstractBone loss due to smoking represents a major risk factor for fractures and bone osteoporosis. Signaling through the aryl hydrocarbon receptor (AhR) and its ligands contributes to both bone homeostasis and inflammatory diseases. It remains unclear whether the same AhR signaling axis affects the temporomandibular joint (TMJ). The aim of this study was to investigate possible mechanisms which mediate bone loss in the TMJ due to smoking. In particular, whether benzo[a]pyrene (B[a]P), a carcinogen of tobacco smoke, induces expression of the AhR target gene, Cyp1a1, in mandibular condyles. Possible functions of an endogenous ligand of FICZ, were also investigated in a TMJ-osteoarthritis (OA) mouse model. B[a]P was administered orally to wild-type and AhR−/− mice and bone metabolism was subsequently examined. TMJ-OA was induced in wild-type mice with forceful opening of the mouth. Therapeutic functions of FICZ were detected with μCT and histology. Exposure to B[a]P accelerated bone loss in the mandibular subchondral bone. This bone loss manifested with osteoclastic bone resorption and upregulated expression of Cyp1a1 in an AhR-dependent manner. In a mouse model of TMJ-OA, FICZ exhibited a dose-dependent rescue of mandibular subchondral bone loss by repressing osteoclast activity. Meanwhile, in vitro, pre-treatment with FICZ reduced RANKL-mediated osteoclastogenesis. B[a]P regulates mandibular subchondral bone metabolism via the Cyp1a1. The AhR ligand, FICZ, can prevent TMJ-OA by regulating osteoclast differentiation.

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