Rui Hua

Osteoarthritis (OA) is the most common chronic joint disease, yet no disease-modifying therapies exist. Synovial inflammation is increasingly recognized as a key driver of OA progression, but its therapeutic targets remain poorly defined. Here we show that selective inhibition of connexin 43 (Cx43) hemichannels (HCs) attenuates OA progression in a murine post-traumatic OA model. AAV-mediated Cx43 deletion reduced cartilage degeneration, synovial inflammation, subchondral bone sclerosis, and pain. We developed a monoclonal antibody, Cx43(M1), that selectively blocks Cx43 HCs without disrupting gap junction communication. Cx43(M1) preserved joint integrity and alleviated OA even when treatment began after cartilage damage was established. The antibody preferentially targeted synovial macrophages, suppressing HC activity, ATP and PGE₂ release, and inflammatory gene expression. Macrophage-specific Cx43 deletion reproduced these effects, and Cx43 HC blockade similarly inhibited inflammatory responses in primary human OA synovial macrophages. These findings identify synovial macrophage Cx43 HCs as promising therapeutic targets for OA.

Clinically, bone mineral density (BMD) accounts for only approximately 50% of the observed variance in bone fragility fractures. This review examines the dynamic and mechanistic role of the non-collagenous organic matrix, specifically proteoglycans (PGs) and glycosaminoglycans (GAGs), in maintaining bone toughness and bone quality. During aging, bulk cortical GAG levels decrease by up to ~17% and are highly associated with reduced bone tissue toughness. We analyze how this age-related loss may arise from uncoupled bone remodeling and tissue aging, including the accumulation of older, interstitial tissue and dysregulated osteocyte-mediated matrix maintenance. We then discuss the functional importance of PG/GAG composition, maturation, and catabolism and how perturbations in these processes can promote pro-inflammatory signaling that accelerates matrix degradation and contributes to systemic aging. Lastly, we discuss potential interventions to preserve or restore GAGs/PGs in bone and improve overall bone quality.

Cell crowding causes high-grade breast cancer cells to become more invasive by activating a molecular switch that causes the cells to shrink and spread.

Antigen-specific immune responses determine the efficacy of herpes simplex virus type 2 (HSV-2) vaccines. To optimize the immunogenicity of the antigen gD2, we developed the gD2ΔUL25 DNA vaccine encoding HSV-2 glycoprotein D and UL25 gene encoding viral capsid vertex proteins in this study. The gD2 and gD2ΔUL25 DNA vaccines were compared with formalin-inactivated HSV-2 (FI-HSV-2), and results showed a greater protective immune response induced by gD2ΔUL25 than by gD2. Therefore, gD2ΔUL25 was chosen to evaluate further using the IL28B adjuvant. Immunization with gD2ΔUL25/IL28B elicited stronger humoral and T cell immune responses than with gD2ΔUL25 alone. Compared with controls, gD2ΔUL25/IL28B decreased HSV-2 viral loads and induced protective effects against genital tract lesions generated by HSV-2. These findings demonstrated that the prophylactic DNA vaccine gD2ΔUL25 with IL28B adjuvant could enhance the humoral and T cell immune responses, and improve the protective immune response against HSV-2 in female mice compared with FI-HSV-2.