Biology subjects

Raulino Lima, J.

Publications and source records attributed to Raulino Lima, J..

2 recordsLinked to original sources

bioRxiv2026

Distinct Biological and Biomechanical Features in TMJ and Knee Cartilages

The temporomandibular joint (TMJ) and the knee joint are two of the most frequently used joints in the body, with the mandibular condylar cartilage (MCC) and the articular cartilage (AC) covering the joint bone surfaces, respectively. Compromised MCC functions lead to various temporomandibular disorders (TMD), including TMJ osteoarthritis (TMJ OA); however, the mechanisms governing MCC homeostasis and its biomechanical properties are still poorly understood. In this study, we comprehensively compared the biological and biomechanical features of the MCC and AC in mice. Histological analysis on P1, P21, 3-month, and 10-month mice revealed the most drastic structural differences between MCC and AC at occlusion establishment (P21), with MCC found to be more susceptible to age-associated cartilage degeneration. Immunostaining revealed differentially distributed cartilage extracellular matrix components in MCC and AC, including collagen type I, II, and X, and highly enriched expression of several key transcriptional factors at the posterior region of the MCC, including sex determining region Y-box 9 (SOX9), runt-related transcription factor 2 (RUNX2), and scleraxis (SCX). The posterior MCC also houses a group of long-lasting, slow-proliferative cells, as evidenced by the BrdU/EdU incorporation assay, suggesting the presence of a potential stem/progenitor cell niche at the posterior TMJ. Unbiased nanoindentation analysis revealed distinct biomechanical features between these joint cartilages. MCC exhibits a significantly lower elastic modulus (EIT) than AC, with the highest EIT observed at the anterior TMJ, which is oppositely associated with the fibrous layer thickness, but positively correlated with the ratio of the collagen type X-positive matrix in the cartilaginous layer. Altogether, this study provides a basic understanding of the biological and biomechanical features of the cartilaginous tissues in two important joints, which may facilitate our understanding of the physiology in the TMJ and knee joint, and support the applications of mouse models to study TMJ dysfunctions.

developmental biology↗

bioRxiv2024

PRMT1-SFPQ regulates intron retention to control matrix gene expression during craniofacial development

Spliceosomopathies, which are a group of disorders caused by defects in the splicing machinery, frequently affect the craniofacial skeleton and limb, but the molecular mechanism underlying this tissue-specific sensitivity remains unclear. Splicing factors and small nuclear ribonucleoproteins (snRNPs) are core components of splicing machinery, and splicing factors are further controlled by post-translational modifications, among which arginine methylation is one of the most prevalent. We determined the splicing mechanisms in the cranial neural crest cells (CNCCs), a multipotent developmental population that gives rise to the majority of the craniofacial skeleton, and focused on an upstream regulator of splicing proteins, protein arginine methyltransferase 1 (PRMT1). PRMT1 is the highest expressing arginine methyltransferase in CNCCs and its role in craniofacial development is evident from our earlier investigation, where CNCC-specific Prmt1 deletion caused cleft palate and mandibular hypoplasia. PRMT1 catalyzes arginine methylation of splicing factors to modify protein localization, expression and activity. In the present study, we uncover roles of PRMT1 in the regulation of intron retention, a type of alternative splicing where introns are retained in the mature mRNA. CNCCs from mandibular primordium of Prmt1-deficient embryos demonstrated an increase in the percentage of intron-retaining mRNA of matrix genes, which triggered NMD, causing a reduction in matrix mRNA abundance. We further identified SFPQ as a substrate of PRMT1 that depends on PRMT1 for arginine methylation and protein expression in the developing craniofacial structures. Depletion of SFPQ in CNCCs phenocopied PRMT1 deletion whereby matrix, Wnt signaling components and neuronal gene transcripts contained higher IR and exhibited lower expression. We further recognized gene length as a common feature among SFPQ-regulated genes in CNCCs. Altogether, these findings demonstrate that the PRMT1-SFPQ pathway modulates matrix gene expression via IR-triggered NMD in CNCCs during craniofacial development.

developmental biology↗