Biology subjects

Lamia, S. N.

Publications and source records attributed to Lamia, S. N..

3 recordsLinked to original sources

bioRxiv2026

Protocol for 3D digital dynamic histomorphometry of bone via time-lapse registration of serial microCT scans

Serial in vivo microCT enables quantification of dynamic bone remodeling by capturing formation and resorption over time. This protocol uses Dragonfly to register pre- and post-intervention scans of rodent long bones through an intuitive drag-and-click workflow that requires no coding expertise. Rigid registration enables spatial mapping and quantification of formed, resorbed, and quiescent cortical and trabecular bone at periosteal and endosteal surfaces across multiple tibial regions, providing a non-destructive and complementary alternative to classic, fluorochrome-based dynamic histomorphometry. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=160 HEIGHT=200 SRC="FIGDIR/small/728585v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@e20e89org.highwire.dtl.DTLVardef@12872fcorg.highwire.dtl.DTLVardef@951694org.highwire.dtl.DTLVardef@1fd52f2_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

The developing tendon and enthesis are hypoxic and rely on hypoxia-inducible factor 1a (Hif1a) during postnatal development

The tendon-bone enthesis is a specialized fibrocartilaginous tissue crucial for muscle-to-bone force transmission, yet its postnatal development is not fully understood. Emerging evidence suggests hypoxia plays a pivotal role in enthesis maturation akin to its function in skeletal growth plates, with Hypoxia Inducible Factor 1 alpha (HIF-1) acting as a key regulator of cellular adaptation (e.g., cell survival, extracellular matrix (ECM) deposition). Here, we investigated the spatial and temporal dynamics of hypoxia in the murine Achilles tendon enthesis and elucidated the role of Hif1a in enthesis cell survival and ECM formation using Scleraxis-lineage conditional knockout (ScxCre; Hif1a cKO) mice. We found that while neonatal tendons rapidly resolve hypoxia after birth, the enthesis maintains a hypoxic niche through postnatal day 5, mirroring a gradient observed in growth plates. Disruption of HIF-1 in enthesis-resident cells resulted in pronounced deficits in grip strength, abnormal tendon-bone attachment morphology, disrupted calcaneal architecture, impaired mineralization, and significant ECM disorganization. Histological analyses revealed persistent cell death and loss of the characteristic fibrocartilaginous gradient in cKO entheses, including dysregulated collagen alignment. In vitro, HIF-1-deficient tendon fibroblasts exhibited blunted transcriptional responses to hypoxia, altered metabolic gene expression, and changes in ECM deposition. Collectively, our findings illuminate hypoxia as a sustained niche in the postnatal enthesis, with HIF-1 critically required for cell survival, ECM organization, and enthesis structural integrity. This work advances our understanding of enthesis biology and provides insights relevant to tendon-bone attachment disorders and regenerative strategies.

developmental biology↗

bioRxiv2023

Optogenetic-Induced Muscle Loading Leads to Mechanical Adaptation of the Achilles Tendon Enthesis in Mice

The growth of the skeleton depends on the transmission of contractile muscle forces from tendon to bone across the extracellular matrix-rich enthesis. Loss of muscle loading leads to significant impairments in enthesis development. However, little is known about how the enthesis responds to increased loading during postnatal growth. To study the cellular and matrix adaptations of the enthesis in response to increased muscle loading, we used optogenetics to induce skeletal muscle contraction and unilaterally load the Achilles tendon and enthesis in young (i.e., during growth) and adult (i.e., mature) mice. In young mice, daily bouts of unilateral optogenetic loading led to expansion of the calcaneal apophysis and growth plate, as well as increased vascularization of the normally avascular enthesis. Daily loading bouts, delivered for 3 weeks, also led to a mechanically weaker enthesis with increased molecular-level accumulation of collagen damage in young mice. However, adult mice did not exhibit impaired mechanical properties or noticeable structural adaptations to the enthesis. We then focused on the transcriptional response of the young tendon and bone following optogenetic-induced loading. After 1 or 2 weeks of loading, we identified, in tendon, transcriptional activation of canonical pathways related to glucose metabolism (glycolysis) and inhibited pathways associated with cytoskeletal remodeling (e.g., RHOA and CREB signaling). In bone, we identified activation of inflammatory signaling (e.g., NFkB and STAT3 signaling) and inhibition of ERK/MAPK and PTEN signaling. Thus, we have demonstrated the utility of optogenetic-induced skeletal muscle contraction to elicit structural, functional, and molecular adaptation of the enthesis in vivo especially during growth.

bioengineering↗