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

Co-administration of aspirin and allogeneic adipose-derived stromal cells attenuates bone loss in ovariectomized rats through the anti-inflammatory and chemotactic abilities of aspirin

Authors

Hao Liu, Wei Li, Yunsong Liu, Xiao Zhang and Yongsheng Zhou

Abstract

Introduction
Osteoporosis is a syndrome of excessive skeletal fragility characterized by the loss of mass and deterioration of microarchitecture in bone. Single use of aspirin or adipose-derived stromal cells (ASCs) has been recognized recently to be effective against osteoporosis. The goal of the study was to evaluate the osteogenic effects of the co-administration of aspirin and allogeneic rat adipose-derived stromal cells (rASCs) on ovariectomized (OVX)-induced bone loss in rats. The underlying mechanisms were investigated in vitro and in vivo.

Methods
Firstly, allogeneic rASCs were isolated and cultured, and the conditioned medium (CM) from the maintenance of rASCs was collected. Secondly, the OVX rats were administrated CM, rASCs, aspirin (ASP) or rASCs + ASP, respectively. Twelve weeks later, the anti-inflammatory and osteogenic effects were assessed by micro-CT, undecalcified histological sections, dynamic histomorphometric analyses and serologic assays for biochemical markers. Finally, a Transwell migration assay in vitro and cell-trafficking analyses in vivo were used to explore the effects of aspirin on rASC migration.

Results
Systemic administration of aspirin and rASCs attenuated OVX-induced bone loss better than single use of aspirin or ASCs (p < 0.05, respectively). Next, we analyzed the underlying mechanisms of the anti-inflammatory and chemotactic abilities of aspirin. Aspirin suppressed serum levels of the pro-inflammatory cytokines on tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and the anti-inflammatory ability was positively associated with bone morphometry. Also, aspirin exhibited excellent chemotactic effects in vitro and accelerated the homing of allogeneic rASCs into bone marrow during early in vivo stages.

Conclusions
Co-administered aspirin and allogeneic ASCs can partially reverse OVX-induced bone loss in rats. This effect appears to be mediated by the anti-inflammatory and chemotactic abilities of aspirin.

Link to Article

http://dx.doi.org/10.1186/s13287-015-0195-x