Influence of Different-Frequency GlucocorticoidInduction on Morphological Structures of Humeri,Soft Tissues and Immune System in Rats

Authors

Li Jian-min, Li Heng

Abstract

Objective: To explore the influence of different-frequency glucocorticoid (GC) induction on morphological structures of humeri and soft tissues as well as immune system in rats. 

Methods: A total of 32 specific pathogen-free (SPF) SD rats at the age of 3 months were selected and randomly divided into 4 groups, 8 cases in each group. The rats in control group were not given any treatment, while those in low-, moderate- and high-frequency groups were treated with intramuscular injection of dexamethasone 1 mg/kg per time for twice, 4 times and 6 times per week, respectively. All the rats were sacrificed on d30 to measure their body mass and qualities of soft tissues and immune organs, and bone histomorphometry was applied to analyze humeral bone mass and bone structural changes.

Results: Compared with control group, there was no change in cancellous bone mass and bone structures of upper humeri in low-frequency group, but serious loss of bone mass, significantly degenerated bone structure, markedly reduced trabecular thickness and number as well as notably increased trabecular separation was all observed in moderate- and high-frequency groups. The size of cortical bones, total size of bone structure, thickness of cortical bones and size percentage of cortical bones in middle humeri reduced apparently, while the size percentage of medullary cavity increased dramatically in high-frequency group. Growth plate thickness of upper humeri decreased in low-, moderate- and high-frequency groups, and the diameters of mastocytes diminished in moderate- and high-frequency groups. Compared with control group, body mass decreased obviously, qualities and indexes of spleen and thymus showed decreasing tendency along with the increase of drug administration frequency in low-, moderate- and high-frequency groups.

Conclusion: Low-frequency GC cannot change humeral morphology. The higher the frequency of drug administration is, the more the loss of cancellous bone mass is. When the frequency reaches to 6 times per week, the loss of cortical and cancellous bones is much severer. However, with the increase of drug administration frequency, thymic degeneration, splenic atrophy and immunosuppression can be induced. Therefore, the influence of different-frequency drug administration on bones and soft tissues in different locations as well as immune function should be fully considered and reasonable drug administration protocols should be designed for the establishment of SD rat models with osteoporosis.

Link to Article

http://scholar.google.com/scholar_url?url=http://www.jitm.hk/CN/article/downloadArticleFile.do%3FattachType%3DPDF%26id%3D196&hl=en&sa=X&scisig=AAGBfm28q6Urn7yc_UONqiUYfhESjzbqFA&nossl=1&oi=scholaralrt

Lifelong challenge of calcium homeostasis in male mice lacking TRPV5 leads to changes in bone and calcium metabolism

Authors

Bram C. J. van der Eerden, W. Nadia H. Koek, Paul Roschger, M. Carola Zillikens, Jan H. Waarsing, Annemiete van der Kemp, Marijke Schreuders-Koedam, Nadja Fratzl-Zelman, Pieter J. M. Leenen, Joost G. J. Hoenderop,
Klaus Klaushofer, René J. M. Bindels and Johannes P.T.M. van Leeuwen

Abstract

Trpv5 plays an important role in calcium (Ca2+) homeostasis, among others by mediating renal calcium reabsorption. Accordingly, Trpv5 deficiency strongly stresses Ca2+ homeostasis in order to maintain stable serum Ca2+. We addressed the impact of lifelong challenge of calcium homeostasis on the bone phenotype of these mice. Aging significantly increased serum 1,25(OH)2D3 and PTH levels in both genotypes but they were more elevated in Trpv5-/- mice, whereas serum Ca2+ was not affected by age or genotype. Age-related changes in trabecular and cortical bone mass were accelerated in Trpv5-/- mice, including reduced trabecular and cortical bone thickness as well as reduced bone mineralization. No effect of Trpv5 deficiency on bone strength was observed. In 78-week-old mice no differences were observed between the genotypes regarding urinary deoxypyridinoline, osteoclast number, differentiation and activity as well as osteoclast precursor numbers, as assessed by flow cytometry. In conclusion, life-long challenge of Ca2+ homeostasis present in Trpv5-/- mice causes accelerated bone aging and a low cortical and trabecular bone mass phenotype. The phenotype of the Trpv5-/- mice suggests that maintenance of adequate circulatory Ca2+ levels in patients with disturbances in Ca2+ homeostasis should be a priority in order to prevent bone loss at older age.

Link to Article

http://www.physiomics.eu/media/210426/j_biol_chem_xx_xx-xx__2016.1.pdf

FGF signaling in the osteoprogenitor lineage non-autonomously regulates postnatal chondrocyte proliferation and skeletal growth

Fibroblast growth factor (FGF) signaling is important for skeletal development; however, cell-specific functions, redundancy and feedback mechanisms regulating bone growth are poorly understood. FGF receptors 1 and 2 (Fgfr1 and Fgfr2) are both expressed in the osteoprogenitor lineage.

Cartilage-specific deletion of ephrin-B2 in mice results in early developmental defects and an osteoarthritis-like phenotype during aging in vivo

Authors

Gladys Valverde-Franco, Bertrand Lussier, David Hum, Jiangping Wu, Adjia Hamadjida, Numa Dancause, Hassan Fahmi, Mohit Kapoor, Jean-Pierre Pelletier and Johanne Martel-Pelletier

Abstract

Background
Ephrins and their related receptors have been implicated in some developmental events. We have demonstrated that ephrin-B2 (EFNB2) could play a role in knee joint pathology associated with osteoarthritis (OA). Here, we delineate the in vivo role of EFNB2 in musculoskeletal growth, development, and in OA using a cartilage-specific EFNB2 knockout (EFNB2Col2KO) mouse model.

Methods
EFNB2Col2KO was generated with Col2a1-Cre transgenic mice. The skeletal development was evaluated using macroscopy, immunohistochemistry, histomorphometry, radiology, densitometry, and micro-computed tomography. Analyses were performed at P0 (birth) and on postnatal days P15, P21, and on 8-week- and 1-year-old mice.

Results
EFNB2Col2KO mice exhibited significant reduction in size, weight, length, and in long bones. At P0, the growth plates of EFNB2Col2KO mice displayed increased type X collagen, disorganized hyphertrophic zone, and decreased mineralization. At P15, mutant mice demonstrated a significant reduction in VEGF and TRAP at the chondro-osseous junction and a delay in the secondary ossification, including a decrease in bone volume and trabecular thickness. At P21 and 8 weeks old, EFNB2Col2KO mice exhibited reduced bone mineral density in the total skeleton, femur and spine. One-year-old EFNB2Col2KO mice demonstrated OA phenotypic features in both the knee and hip. By P15, 27 % of the EFNB2Col2KO mice developed a hip locomotor phenotype, which further experiments demonstrated reflected the neurological midline abnormality involving the corticospinal tract.

Conclusion
This in vivo study demonstrated, for the first time, that EFNB2 is essential for normal long bone growth and development and its absence leads to a knee and hip OA phenotype in aged mice.

Link to Article

http://dx.doi.org/10.1186%2Fs13075-016-0965-6

Clinical, Radiographic, and Histologic Evaluation of Maxillary Sinus Lift Procedure Using a Highly Purified Xenogenic Graft (Laddec®)

Authors

Guarnieri R, Belleggia F, Ippoliti S, DeVilliers P, Stefanelli LV, Di Carlo S, Pompa G

Abstract

Objectives: The aim of this study was to evaluate the clinical, radiographic and histologic results when a highly purified xenogenic bone (Laddec®) was used as grafting material in maxillary sinuses.

Material and Methods: In fifteen patients requiring unilateral maxillary sinus augmentation, the grafting procedure was performed with Laddec®. Forty-two implants were installed after a 6 month healing period. The height of the augmented sinus was measured radiographically immediately after augmentation and postoperatively up to 36 months. At the time of implant placement, a bone core was harvested in each patient for histological examination.

Results: The cumulative implant survival rate was 97.6%. The original height was 3.65 (SD 0.7) mm and the augmented sinus height was 13.8 (SD 1.4) mm after the surgery. The reduced height of grafted xenogenic material (RDL) at the implant insertion was 0.83 (SD 0.38) mm, and at the final postoperative visit was 0.91 (SD 0.25) mm, showing no significant correlation with the follow-up periods by Spearman’s test (P = 0.118). In addition, no significant difference in the RDL was observed according to the site of implantation (P = 0.682). The mean implant marginal bone loss was 0.38 (SD 0.24) mm. Histological analysis showed the bone cores were composed of 64.72 (SD 3.44)% newly formed bone, 17.41 (SD 2.02)% connective tissue, 16.93 (SD 2.83)% residual graft particles, and 0.94 (SD 0.11)% inflammatory cells.

Conclusions: According to our data, the highly purified xenogenic bone (Laddec®), used as graft material in the sinus lift procedure, may create adequate bone volume, and appropriate osseointegration of dental implants.

Link to Article

http://dx.doi.org/10.5037/jomr.2016.7103

Sorting Nexin 27 couples PTHR trafficking to retromer for signal regulation in osteoblasts during bone growth

The parathyroid hormone 1 receptor (PTHR) is central to the process of bone formation and remodelling. PTHR signaling requires receptor internalisation into endosomes, which is then terminated by recycling or degradation. Here we show that sorting nexin 27 (SNX27) functions as an adaptor that couples PTHR to the retromer trafficking complex.