Osteoimmunology articles from across Nature Portfolio

In their previous study, the researchers systematically revealed that endplate sclerosis is a significant aspect of spine degeneration or aging and a primary source of spinal pain. However, the underlying mechanisms of endplate sclerosis remained unclear. In their current report, it is shown that senescent cells accumulate in the sclerotic endplates of lumbar spine instability (LSI) or aging mouse models. The clearance of these senescent cells was found to restrain angiogenesis coupled with endplate sclerosis. Notably, macrophages were identified as undergoing senescence in the sclerotic endplates. The specific knockout of cdkn2a (p16) in macrophages abrogated LSI or aging-induced angiogenesis and sclerosis in the endplates. Moreover, both in vivo and in vitro studies indicated that IL-10 mediates the effects of senescent macrophages on angiogenesis and sclerosis in the endplates. Overall, these findings suggest that senescent macrophages orchestrate angiogenesis coupling with endplate sclerosis via the IL-10/pSTAT3 axis. This study enhances the understanding of the connection between immune senescence and endplate sclerosis and uncovers senescent macrophage-initiated endplate sclerosis as potential therapeutic targets for spinal degeneration.

Three-dimensional analysis of the intact bone marrow within whole long bones remains very challenging. Here, the authors present a method that stabilizes the marrow and provides subcellular resolution of fluorescent signals throughout the murine femur.

Denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, previously developed for osteoporosis, was shown to be effective at inducing structural modification in patients with erosive hand osteoarthritis after 24 weeks.

ETS1 regulates tissue-remodeling properties of specific fibroblast subtypes in the synovium, gut and cancer and thus emerges as a novel cross-tissue therapeutic target for modulation of pathogenic fibroblast activation.

Comprehensive review articles written by international experts are important to provide readers from diverse backgrounds with an expanding knowledge base.

Probiotic microorganisms such as Lactobacillus rhamnosus can protect from bone loss by enhancing levels of butyrate, which leads to the expansion of regulatory T cells. These stimulate CD8⁺ T cells to secrete WNT10b, a bone anabolic factor.

A variety of biologic DMARDs now exist for the treatment of rheumatoid arthritis, but we don’t really know how these drugs function in vivo. Can time-lapse intravital imaging distinguish the modes of action of DMARDs by comparing response to joint destruction in mouse models of arthritis?

Biologic agents targeting key proteins involved in bone homeostasis are revolutionizing the management of osteoporosis. New clinical data support the use of these novel therapies to rapidly increase bone mass and decrease the risk of fractures.