Masayuki Tsukasaki

The immune system evolved to efficiently eradicate invading bacteria and terminate inflammation through balancing inflammatory and regulatory T-cell responses. In autoimmune arthritis, pathogenic T_H17 cells induce bone destruction and autoimmune inflammation. However, whether a beneficial function of T-cell-induced bone damage exists is unclear. Here, we show that bone-damaging T cells have a critical function in the eradication of bacteria in a mouse model of periodontitis, which is

Osteoprotegerin (OPG) is a circulating decoy receptor for RANKL, a multifunctional cytokine essential for the differentiation of tissue-specific cells in bone and immune systems such as osteoclasts, medullary thymic epithelial cells (mTECs), and intestinal microfold cells (M cells). However, it is unknown whether OPG functions only at the production site or circulates to other tissues acting in an endocrine fashion. Here we explore the cellular source of OPG by generating OPG-floxed mice and sho

The ontogeny and fate of stem cells have been extensively investigated by lineage-tracing approaches. At distinct anatomical sites, bone tissue harbors multiple types of skeletal stem cells, which may independently supply osteogenic cells in a site-specific manner. Periosteal stem cells (PSCs) and growth plate resting zone stem cells (RZSCs) critically contribute to intramembranous and endochondral bone formation, respectively. However, it remains unclear whether there is functional crosstalk be

Osteoclasts are the exclusive bone-resorbing cells that have a central role in bone homeostasis as well as bone destruction in cancer and autoimmune disease. Both mouse and human genetic studies have clearly proven that receptor activator of NF-κB ligand (RANKL; encoded by the Tnfsf11 gene) and its receptor RANK are essential for osteoclastogenesis. Although there have been several reports on RANKL-independent osteoclastogenesis, previous studies have never provided in vivo evidence showing RANK

Osteoclasts, the only cells that can resorb bone, play a central role in bone homeostasis as well as bone damage under pathological conditions such as osteoporosis, arthritis, periodontitis, and bone metastasis. Recent studies using single-cell technologies have uncovered the regulatory mechanisms underlying osteoclastogenesis at unprecedented resolution and shed light on the possibility that there is heterogeneity in the origin, function, and fate of osteoclast-lineage cells. Here, we discuss t

Cancer-bone interactions have been investigated primarily in the context of bone metastasis. However, hematogenous spread is not the only route by which cancer cells enter the bone. Certain types of cancer, including head and neck squamous cell carcinoma (HNSCC), directly invade the bone tissue because of the close anatomical relationship between the bone and primary lesions. This type of invasion significantly worsens prognosis and quality of life; however, comparatively less attention has been

In Brief: The authors use cell tracing approaches in a PRMT5flox/Δ Ctsk-Cre strain to label periosteal stem cells (PSCs) and show that PSCs are not only essential for intramembranous bone formation but also for endochondral bone formation. The study identifies the role of PSC derived indian hedgehog (Ihh) in maintaining growth plate homeostasis and postnatal skeletal growth.

Decades of research into the immune regulation of cancer have revolutionized oncology, leading to the clinical success of immune checkpoint inhibitors. In contrast, the roles of nonimmune systems in tumor regulation remain largely undefined. Our recent study of cancer bone invasion has uncovered a previously unrecognized host defense mechanism: stromal cells in the periosteum, the membranous tissue enveloping the bone, actively respond to tumor proximity and facilitate periosteum thickening that