10th International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems

The first day of the conference chaired by Iannis Adamopoulos and Hiroshi Takayanagi highlighted how rapidly the field of osteoimmunology is expanding beyond classical bone resorption and formation, toward a more integrated view of bone as a dynamic immune, vascular, metabolic and stem cell organ.Across Sessions I and II, speakers explored how specialized niches in bone marrow, growth plate, vasculature and stromal compartments shape skeletal homeostasis, inflammation, regeneration and disease.The session opened with Noriaki Ono who presented new insights into the endosteal niche at the crossroads of bone and immune cells.Building on the concept that PTHrP positive resting zone chondrocytes serve as skeletal stem cells in the postnatal growth plate, his talk emphasized how PTHrP controls the orderly transition of chondrocyte differentiation and prevents ectopic hypertrophic conversion through GDF5 pathways.Andrei Chagin further expanded this theme by describing a dual stem cell organization in growth plates.His presentation distinguished two resting zone stem cell subsets, including a Wnt enriched, highly stem like GP1 population and a GP2 population marked by different molecular features.This concept provides a new framework for understanding how the growth plate sustains longitudinal bone growth while balancing stemness, proliferation and hypertrophic differentiation.Anjali Kusumbe's lecture focused on skeletal vasculature and vascular niches, emphasizing endothelial diversity across space, time and function.Her work has been central to defining specialized bone vessels as niche structures that regulate bone formation, hematopoiesis and tissue aging.Earlier studies showed that age associated decline of niche forming skeletal vessels can impair bone and hematopoietic environments, while more recent work continues to reveal site specific vascular and stromal heterogeneity in skull, vertebral and long bone marrow niches.The second session shifted toward inflammatory and regenerative mechanisms in stromal, stem and progenitor cell biology.Masayuki Tsukasaki presented a vascular derived RANKL and OPG axis controlling arterial calcification independently of the skeleton, illustrating how classical bone regulatory molecules can act in vascular disease.Ritu Chakravarti introduced multilevel regulation of osteoclastogenesis by 14-3-3ζ at the inflammation and bone interface.Several talks emphasized bone as an active systemic responder to inflammation.Stavroula Kousteni described bone-derived inflammatory SAA1 as a regulator of stem cell state and persistence in myeloid malignancies.Yasuhiro Kobayashi addressed inflammaging, focusing on endothelial RANK signaling.A recurring theme was the intimate connection between immune cells and skeletal repair.Salwa Suliman and colleagues highlighted regulatory T cells as orchestrators of mesenchymal stromal cell mediated bone regeneration.Kazutaka Nakamura and colleagues described a stromal niche supporting osteoclastogenesis in giant cell tumor of bone.Daniela Paternina Martinez showed that IL 17RA blockade can uncover alternative osteogenic pathways driven by IL 17F through BMP and Wnt signaling.Jessica De Angelis presented evidence that bone can rapidly sense inflammation and secrete Lipocalin 2, reinforcing the concept that skeletal tissue participates actively in immune communication.Together, the session portrayed bone as a highly organized, immune responsive and metabolically adaptable organ.Stem cells, stromal cells, endothelial cells, immune cells and osteoclasts do not act in isolation.They form interconnected niches that determine skeletal growth, inflammatory bone loss, regeneration, vascular calcification, aging and malignancy.This integrated view captures the current direction of osteoimmunology: from bone and immune crosstalk toward a broader biology of tissue niches, systemic inflammation and organ level adaptation. Day 2: New insights in Osteoclast biology, Inflammation and BoneDay 2, chaired by Gerhard Krönke and Dirk Elewaut, began with a session focused entirely on osteoclasts.Yuji Mishina discussed modes by which osteoclasts control osteoblasts, including direct contact that leads to osteoblast cell death in vivo.He showed data indicating that this communication is largely by transfer of specific proteins, suggesting that interruption of this mechanism might preserve bone mass.Next, we were introduced to the role of super-enhancer derived RNAs in osteoclasts by Kyung Park-Min.Her group used human osteoclast cultures to find osteoclast-specific actively produced transcripts, and showed that some of these non-coding RNAs control originating from the NFATc1 and MYC super-enhancers control osteoclastogenesis.The next step will be to determine if this new mode of regulation is altered in disease states such as rheumatoid arthritis.Aline Bozec delved into metabolism by osteoclasts, describing roles for L-arginine and Lornithine in inflammatory bone loss.Interestingly, she showed that L-ornithine increases synthesis of the neurotransmitter GABA, which acts via binding to β-catenin, to decrease osteoclastogenesis.Fanxin Long also delved into the bioenergetics of osteoclasts, focusing on the glucose transporter Glut1 and fatty acid oxidation.His work follows previous studies showing significant sex differences in the mouse models that remain incompletely explained.We learned about lysosomal transporters in osteoclasts from Nathan Pavlos.These organelles are critical to the bone resorption by osteoclasts, but not all highly expressed transporters control this function.Ara Nazarian took a completely different approach, describing an integrated computational model coupling mechanical regulation with biological healing.He noted that most models skip the soft callus phase when important inflammation occurs and emphasized the importance of "ground truth" experimental data.Gabriel Mbalaviele took us deeper into the mechanisms of inflammation and regulation of bone mass, focusing on pyroptosis, an inflammatory cell death.He first described the surprising result that low-dose LPS stimulates periosteal, but not endosteal, bone formation by causing cell death in the bone marrow, dependent on GSDMD.He next showed that deficiency in GSDME, a mediator of inflammasome-independent pyroptosis, leads to age-associated bone loss.The take-home message is that pyroptosis can have either beneficial or harmful effects on bone, depending on the gasdermin and biological context.The day ended with short talks by Carina Scholtysek and Sanya Novak.Carina continued the metabolism theme, discussing the role of Nrf1 in driving osteoclast differentiation using conditional knockout mice.Sanya added to the discussion of inflammation by describing a novel CD115+Adgre+ osteoclast progenitor population. Day 3: Advances in ArthritisSessions on the third day chaired by Mary Nakamura and Masayuki Tsukasaki were focused on osteoimmune roles in inflammatory and degenerative arthritis along with talks demonstrating critical interactions between the central and peripheral nervous system and bone.The session opened with an exciting discussion by Aristotelis Tsirigos regarding use of artificial intelligence with imaging and -omics technologies to decode the microenvironment and gene regulation to advance studies in precision medicine.He showed how models are being built to construct virtual cells to simulate, predict, and steer cell behavior, with the eventual goal of Downloaded from academic.oup.com