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Systemic administration of strontium or NBD peptide ameliorates early stage cartilage degradation of mouse mandibular condyles.

ABSTRACT: OBJECTIVE:To determine whether mandibular condylar cartilage degradation induced by experimentally abnormal occlusion could be ameliorated via systemic administration of strontium or NBD peptide. METHODS:Six-week-old female C57BL/6J mice were used. From the seventh day after mock operation or unilateral anterior crossbite (UAC) treatment, the control and UAC mice were further respectively pharmacologically treated for 2 weeks or 4 weeks of saline (CON + Saline and UAC + Saline groups), SrCl2 (CON + SrCl2 and UAC + SrCl2 groups) or NBD peptide (CON + NBD peptide and UAC + NBD peptide groups). Changes in condylar cartilage and subchondral bone were assessed 21 and 35 days after mock operation or UAC procedure by histology and micro-CT. Real-time PCR and/or immunohistochemistry (IHC) were performed to evaluate changes in expression levels of col2a1, aggrecan, ADAMTS-5, tnf-?, il-1?, nfkbia, nuclear factor-kappaB phospho-p65 in condylar cartilage, and rankl/rank/opg in both condylar cartilage and subchondral bone. RESULTS:Cartilage degradation with decreased col2a1 and aggrecan expression, and increased ADAMTS-5, tnf-?/il1-?, nfkbia and NF-?B phospho-p65 was observed in UAC + Saline groups. Subchondral bone loss with increased osteoclast numbers and decreased opg/rankl ratio was found in UAC + Saline groups compared to age-match CON + Saline groups. Cartilage degradation and subchondral bone loss were reversed by treatment of SrCl2 or NBD peptide while the same dosage in control mice induced few changes in condylar cartilage and subchondral bone. CONCLUSIONS:The results demonstrate reverse effect of systemic administration of strontium or NBD peptide on UAC-induced condylar cartilage degradation and subchondral bone loss.

SUBMITTER: Liu YD

PROVIDER: S-EPMC4695290 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Systemic administration of strontium or NBD peptide ameliorates early stage cartilage degradation of mouse mandibular condyles.

Liu Y-D YD Yang H-X HX Liao L-F LF Jiao K K Zhang H-Y HY Lu L L Zhang M M Zhang J J He J-J JJ Wu Y-P YP Chen Di D Wang M-Q MQ

Osteoarthritis and cartilage 20150806 1

<h4>Objective</h4>To determine whether mandibular condylar cartilage degradation induced by experimentally abnormal occlusion could be ameliorated via systemic administration of strontium or NBD peptide.<h4>Methods</h4>Six-week-old female C57BL/6J mice were used. From the seventh day after mock operation or unilateral anterior crossbite (UAC) treatment, the control and UAC mice were further respectively pharmacologically treated for 2 weeks or 4 weeks of saline (CON + Saline and UAC + Saline gro ...[more]

PMID: 26256766

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Project description:The shape and volume of the condyle is considered to play an important role in the pathogenesis of the mandibular deviation. Curvature analysis is informative for objectively assess whether the shape of the condyles matches that of the glenoid fossa. In this study, a three-dimensional (3-D) quantification of bilateral asymmetrical condyles was firstly conducted to identify the specific role of 3-D condylar configuration for mandibular asymmetry.55 adult patients, 26 males (26?±?5 yrs) and 29 females (26?±?5 yrs), diagnosed with mandibular asymmetry were included. The examination of deviation of chin point, deviation of dental midlines, inclination of occlusal plane, and depth of the mandibular occlusal plane were conducted. After the clinical investigation, computed tomography images from the patients were used to reconstruct the 3-D mandibular models. Then the condylar volume, surface size, surface curvature and bone mineral density were evaluated independently for each patient on non-deviated and deviated sides of temporomandibular joint.Both the condylar surface size and volume were significantly larger on deviated side (surface size: 1666.14?±?318.3 mm2, volume: 1981.5?±?418.3 mm3). The anterior slope of the condyle was flatter (0.12?±?0.06) and the posterior slope (0.39?±?0.08) was prominently convex on the deviated side. The corresponding bone mineral density values were 523.01 ±118.1 HU and 549.07 ±120. 6 HU on anterior and posterior slopes.The incongruence presented on the deviated side resulted in a reduction in contact areas and, thus, an increase in contact stresses and changes of bone density. All aforementioned results suggest that the difference existing between deviated and non-deviated condyles correlates with facial asymmetrical development. In mandibular asymmetry patients, the 3-D morphology of condyle on deviated side differ from the non-deviated side, which indicates the association between asymmetrical jaw function and joint remodeling.

Project description:ObjectiveKnee osteoarthritis (KOA) is a highly prevalent musculoskeletal disorder characterized by degeneration of cartilage and abnormal remodeling of subchondral bone (SCB). Teriparatide (PTH (1-34)) is an effective anabolic drug for osteoporosis (OP) and regulates osteoprotegerin (OPG)/receptor activator of nuclear factor ligand (RANKL)/RANK signaling, which also has a therapeutic effect on KOA by ameliorating cartilage degradation and inhibiting aberrant remodeling of SCB. However, the mechanisms of PTH (1-34) in treating KOA are still uncertain and remain to be explored. Therefore, we compared the effect of PTH (1-34) on the post-traumatic KOA mouse model to explore the potential therapeutic effect and mechanisms.MethodsIn vivo study, eight-week-old male mice including wild-type (WT) (n = 54) and OPG-/- (n = 54) were investigated and compared. Post-traumatic KOA model was created by destabilization of medial meniscus (DMM). WT mice were randomly assigned into three groups: the sham group (WT-sham; n = 18), the DMM group (WT-DMM; n = 18), and the PTH (1-34)-treated group (WT-DMM + PTH (1-34); n = 18). Similarly, the OPG-/- mice were randomly allocated into three groups as well. The designed mice were executed at the 4th, 8th, and 12th weeks to evaluate KOA progression. To further explore the chondro-protective of PTH (1-34), the ATDC5 chondrocytes were stimulated with different concentrations of PTH (1-34) in vitro.ResultsCompared with the WT-sham mice, significant wear of cartilage in terms of reduced cartilage thickness and glycosaminoglycan (GAG) loss was detected in the WT-DMM mice. PTH (1-34) exhibited cartilage-protective by alleviating wear, retaining the thickness and GAG contents. Moreover, the deterioration of the SCB was alleviated and the expression of PTH1R/OPG/RANKL/RANK were found to increase after PTH (1-34) treatment. Among the OPG-/- mice, the cartilage of the DMM mice displayed typical KOA change with higher OARSI score and thinner cartilage. The damage of the cartilage was alleviated but the abnormal remodeling of SCB didn't show any response to the PTH (1-34) treatment. Compared with the WT-DMM mice, the OPG-/--DMM mice caught more aggressive KOA with thinner cartilage, sever cartilage damage, and more abnormal remodeling of SCB. Moreover, both the damaged cartilage from the WT-DMM mice and the OPG-/--DMM mice were alleviated but only the deterioration of SCB in WT-DMM mice was alleviated after the administration of PTH (1-34). In vitro study, PTH (1-34) could promote the viability of chondrocytes, enhance the synthesis of extracellular matrix (ECM) (AGC, COLII, and SOX9) at the mRNA and protein level, but inhibit the secretion of inflammatory cytokines (TNF-α and IL-6).ConclusionBoth wear of the cartilage was alleviated and aberrant remodeling of the SCB was inhibited in the WT mice, but only the cartilage-protective effect was observed in the OPG-/- mice. PTH (1-34) exhibited chondro-protective effect by decelerating cartilage degeneration in vivo as well as by promoting the proliferation and enhancing ECM synthesis of chondrocytes in vitro. The current investigation implied that the rescue of the disturbed SCB is dependent on the regulation of OPG while the chondro-protective effect is independent of modulation of OPG, which provides proof for the treatment of KOA.The translational potential of this articleSystemic administration of PTH (1-34) could exert a therapeutic effect on both cartilage and SCB in different mechanisms to alleviate KOA progression, which might be a novel therapy for KOA.

Project description:The Fgfr2c C342Y/+ Crouzon syndrome mouse model carries a cysteine to tyrosine substitution at amino acid position 342 (Cys342Tyr; C342Y) in the fibroblast growth factor receptor 2 (Fgfr2) gene equivalent to a FGFR2 mutation commonly associated with Crouzon and Pfeiffer syndromes in humans. The Fgfr2c C342Y mutation results in constitutive activation of the receptor and is associated with upregulation of osteogenic differentiation. Fgfr2cC342Y/+ Crouzon syndrome mice show premature closure of the coronal suture and other craniofacial anomalies including malocclusion of teeth, most likely due to abnormal craniofacial form. Malformation of the mandible can precipitate a plethora of complications including disrupting development of the upper jaw and palate, impediment of the airway, and alteration of occlusion necessary for proper mastication. The current paradigm of mandibular development assumes that Meckel's cartilage (MC) serves as a support or model for mandibular bone formation and as a template for the later forming mandible. If valid, this implies a functional relationship between MC and the forming mandible, so mandibular dysmorphogenesis might be discerned in MC affecting the relationship between MC and mandibular bone. Here we investigate the relationship of MC to mandible development from the early mineralization of the mandible (E13.5) through the initiation of MC degradation at E17.7 using Fgfr2c C342Y/+ Crouzon syndrome embryos and their unaffected littermates (Fgfr2c +/+ ). Differences between genotypes in both MC and mandibular bone are subtle, however MC of Fgfr2c C342Y/+ embryos is generally longer relative to unaffected littermates at E15.5 with specific aspects remaining relatively large at E17.5. In contrast, mandibular bone is smaller overall in Fgfr2c C342Y/+ embryos relative to their unaffected littermates at E15.5 with the posterior aspect remaining relatively small at E17.5. At a cellular level, differences are identified between genotypes early (E13.5) followed by reduced proliferation in MC (E15.5) and in the forming mandible (E17.5) in Fgfr2c C342Y/+ embryos. Activation of the ERK pathways is reduced in the perichondrium of MC in Fgfr2c C342Y/+ embryos and increased in bone related cells at E15.5. These data reveal that the Fgfr2c C342Y mutation differentially affects cells by type, location, and developmental age indicating a complex set of changes in the cells that make up the lower jaw.

Dataset Information

Systemic administration of strontium or NBD peptide ameliorates early stage cartilage degradation of mouse mandibular condyles.

Publications

Systemic administration of strontium or NBD peptide ameliorates early stage cartilage degradation of mouse mandibular condyles.

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