Bone homeostasis involves bone resorption (destruction), which is mediated by osteoclasts, followed by bone reformation, mediated by osteoblasts. This study reveals that semaphorin 4D expressed by osteoclasts is integral to the communication between the two cell types. Using in vitro assays and genetic mouse models, the authors observed that semaphorin 4D suppresses bone formation. This was mediated through semaphorin 4D binding to its receptor plexin B1 on the surface of osteoblasts, leading to activation of RHOA and its downstream effector, RHO kinase (ROCK). This, in turn, led to increased osteoblast motility (and thereby repulsion of osteoblasts from the bone surface) and inhibition of insulin growth factor 1 (IGF1) signalling (which inhibited osteoblast differentiation). Finally, blocking the interaction of semaphorin 4D and plexin B1 promoted bone formation in vivo, indicating that this protein may be a therapeutic target for osteoporosis.