Feng, H. C. | Search bioRxiv

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↗

bioRxiv2023

Spatial Transcriptomics Reveals the Requirement of ADGRG6 in Maintaining Chondrocyte Homeostasis in Mouse Growth Plates

The growth plate is essential for maintaining skeletal growth; however, the mechanisms governing postnatal growth plate homeostasis are poorly understood. Here we show that ADGRG6/GPR126, a cartilage-enriched G protein-coupled receptor (GPCR), is dispensable for embryonic limb development but is required for postnatal growth plate homeostasis. Adgrg6 ablation in osteochondral progenitor cells or postnatal chondrocytes leads to reduced cellularity and impaired maintenance of the resting zone in the growth plate, coupled with increased cell death and reduced cell proliferation. Adgrg6 mutant growth plates also exhibit disorganized extracellular matrix structures and dysregulated hypertrophic differentiation. Furthermore, using a novel spatial transcriptomics workflow that applies to FFPE tissue sections of mineralized mouse knee joints, we demonstrate that Adgrg6 ablation leads to reduced SOX9 expression, induced Indian hedgehog (IHH) signaling, and a precocious chondrogenic-to-osteogenic conversion of the growth plate chondrocytes that may be driven by increased POSTN/integrin receptor signaling. We further demonstrated that ADGRG6 regulates the proper formation of the resting zone growth plate by maintaining the PTHrP and SOX9-positive cell populations. Altogether, our findings elucidate the essential role of ADGRG6 in maintaining chondrocyte fate, survival, and homeostasis of the postnatal growth plates.

molecular biology↗