Biology subjects

Javaheri, B.

Publications and source records attributed to Javaheri, B..

4 recordsLinked to original sources

bioRxiv2026

Regulation and function of trans-physeal growth plate bridges: evidence for a mechanical base isolation role to minimise epiphyseal shear stress

The cartilaginous growth plate (GP) is responsible for all bone elongation during post-natal growth yet must simultaneously contribute to mechanical epiphyseal stability for articulation. How the GP balances these dual functions across the bone-cartilage-bone epiphyseal interface during complex load-growth transitions is not defined. Herein, we examine regulation and mechanobiology of GP bridges - mineralised trans-physeal GP structures - to explore whether they serve these dual GP functions. We have determined the effects of age and sex, short- and long-term joint loading and several established and new osteotropic pharmacological agents on mouse tibial GP bridge number and areal density using micro-computed tomography. We also explored temporal formation and progression of GP bridges by serial in vivo scanning and we imaged epiphyseal load-transfer in young and mature mice in situ via synchrotron X-ray computed tomography (sCT) of intact joints under physiologically oriented load. Our utilisation of digital volume correlation revealed regional 3D load-induced strain inhomogeneities in the GP that are synchronised to bridge location and this was substantiated using finite element modelling. Furthermore, direct micro- and sCT examinations showed that bridges consistently contain a singular epiphyseal/metaphyseal discontinuity which appear to serve a novel mechanical base isolation role to minimise shear stress across the GP. Our data indicate that bridges are regulatable, dynamic structures that synchronise GP strains and exhibit sensitivity to local joint mechanics. We highlight that trans-physeal bridges may contribute to longitudinal bone growth cessation whilst simultaneously stabilising the epiphysis by absorbing compression and shear strains.

bioengineering↗

bioRxiv2021

A New Straightforward Method for Automated Segmentation of Trabecular Bone from Cortical Bone in Diverse and Challenging Morphologies

Many physiological, biomechanical, evolutionary and clinical studies that explore skeletal structure and function require successful separation of trabecular from cortical compartments of a bone that has been imaged by X-ray micro-computed tomography (microCT) prior to analysis. Separation is often time-consuming, involves user bias and needs manual sub-division of these two similarly radio-opaque compartments. We have developed an objective, automated protocol which reduces user bias and enables straightforward, user-friendly segmentation of trabecular from cortical bone without requiring sophisticated programming expertise. This method can conveniently be used as a "recipe" in commercial programmes (Avizo herein) and applied to a variety of datasets. Here, we characterise and share this recipe, and demonstrate its application to a range of murine and human bone types, including normal and osteoarthritic specimens, and bones with distinct embryonic origins and spanning a range of ages. We validate the method by testing inter-user bias during the scan preparation steps and confirm utility in the architecturally challenging analysis of growing murine epiphyses. We also report details of the recipe, so that other groups can readily re-create a similar method in open access programs. Our aim is that this method will be adopted widely to create a more standardized and time efficient method of segmenting trabecular and cortical bone.

physiology↗

bioRxiv2020

Characterisation of growth plate dynamics in murine models of osteoarthritis

BackgroundThe purpose of this study was to investigate growth plate dynamics in surgical and loading murine models of osteoarthritis, to understand whether abnormalities in these dynamics predict osteoarthritis vulnerability. Methods8-week-old C57BL/6 male mice underwent destabilisation of medial meniscus (DMM) (n = 8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice (n = 6), osteoarthritis was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage and growth plate was confirmed by histology and immunohistochemistry. Tibial subchondral bone parameters were measured using microCT and correlated to 3D GP bridging analysis. ResultsHigher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial articular cartilage chondrocytes of DMM and loaded mice. In tibial growth plate, Col10a1 and MMP13 expressions were widely dispersed in a significantly enlarged zones of proliferative and hypertrophic chondrocytes in DMM (p=0.002 and p<0.0001, respectively) and loaded (both p<0.0001) tibiae of mice compared to their controls. 3D quantification revealed enriched growth plate bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. Growth plate dynamics were associated with higher subchondral bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints and epiphyseal trabecular bone volume fraction in medial tibiae of loaded knee joints. ConclusionsThe results confirm articular cartilage chondrocyte transiency in a surgical and loaded murine model of osteoarthritis. Herein, we reveal for the first time spatial variation of growth plate bridging in surgical and loaded osteoarthritis models and how these may contribute to anatomical variation in vulnerability of osteoarthritis development.

physiology↗

bioRxiv2019

Meniscal and ligament modifications in spontaneous and post-traumatic mouse models of osteoarthritis

Osteoarthritis (OA) is a whole joint disease that affects all joint tissues, with changes in the articular cartilage (AC), subchondral bone and synovium. Pathologies in menisci and ligaments, however, are rarely analysed, although both are known to play vital roles in the mechanical stability of the joint. The aim of our study was to describe the pathological changes in menisci and ligament during disease development in murine spontaneous and post-traumatic surgically-induced OA and to quantify tissue mineralisation in the joint space using {micro}CT imaging during OA progression. Knees of Str/ort mice (spontaneous OA model; 26-40wks) and C57CBA F1 mice following destabilisation of medial meniscus (DMM) surgery (post-traumatic OA model; 8wks after DMM), were used to assess histological meniscal and ligament pathologies. Joint space mineralised tissue volume was quantified by {micro}CT. Meniscal pathological changes in Str/ort mouse knees were associated with articular cartilage lesion severity. These meniscal changes included ossification, hyperplasia, cell hypertrophy, collagen type II deposition and SOX9 expression in the fibrous region near the attachment to the knee joint capsule. Anterior cruciate ligaments exhibited extracellular matrix changes and chondrogenesis particularly at the tibial attachment site, and ossification was seen in collateral ligaments. Similar changes were confirmed in the post-traumatic DMM model. {micro}CT analysis showed increased joint space mineralised tissue volume with OA progression in both the post-traumatic and spontaneous OA models. Modifications in meniscal and ligament mineralisation and chondrogenesis are seen with overt AC degeneration in murine OA. Although the aetiology and the consequences of such changes remain unknown, they will influence stability and load transmission of the joint and may therefore contribute to OA progression. In addition, these changes may have important roles in movement restriction and pain, which represent major human clinical symptoms of OA. Description of such soft tissue changes, in addition to AC degradation, should be an important aspect of future studies in mouse models in order to furnish a more complete understanding of OA pathogenesis. Summary statementThis manuscript describes histological changes in mouse knee joints in two models of osteoarthritis and correlates joint space mineralised tissue volume measured by {micro}CT with disease severity.

pathology↗