2022
Loss of chaperone-mediated autophagy is associated with low vertebral cancellous bone mass
Akel N, MacLeod R, Berryhill S, Laster D, Dimori M, Crawford J, Fu Q, Onal M. Loss of chaperone-mediated autophagy is associated with low vertebral cancellous bone mass. Scientific Reports 2022, 12: 3134. PMID: 35210514, PMCID: PMC8873216, DOI: 10.1038/s41598-022-07157-9.Peer-Reviewed Original ResearchConceptsProtein degradation pathwaysRole of CMACRISPR-Cas9-based genome editingChaperone-mediated autophagySkeletal homeostasisDegradation pathwayProteome remodelingMouse genomeGene trapCytoplasmic proteinsOsteoblastic cell lineGenome editingProteasomal degradationSpecific knockdownWild-type controlsCell typesLAMP2ACultured cellsOsteoblast formationCell linesRANKL expressionCathepsin K.Pathophysiological conditionsAutophagyCMA process
2021
Deletion of a putative promoter-proximal Tnfsf11 regulatory region in mice does not alter bone mass or Tnfsf11 expression in vivo
MacLeod RS, Meyer MB, Xiong J, Cawley KM, Liu Y, Onal M, Benkusky NA, Thostenson JD, Pike JW, O’Brien C. Deletion of a putative promoter-proximal Tnfsf11 regulatory region in mice does not alter bone mass or Tnfsf11 expression in vivo. PLOS ONE 2021, 16: e0250974. PMID: 33970941, PMCID: PMC8109787, DOI: 10.1371/journal.pone.0250974.Peer-Reviewed Original ResearchConceptsMonths of ageParathyroid hormoneBone massVitamin D3Osteoclast formationLumbar vertebraeElevated parathyroid hormoneSympathetic nervous systemPathological bone resorptionCultured stromal cellsWild-type littermatesFourth lumbar vertebraFifth lumbar vertebraMRNA abundanceLymph nodesLymphocyte productionBone resorptionCytokine RANKLT lymphocytesKnockout miceBone marrowNervous systemStromal cellsNormal physiological conditionsMaximal stimulation
2020
Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence
Kim HN, Xiong J, MacLeod RS, Iyer S, Fujiwara Y, Cawley KM, Han L, He Y, Thostenson JD, Ferreira E, Jilka RL, Zhou D, Almeida M, O'Brien CA. Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence. JCI Insight 2020, 5: e138815. PMID: 32870816, PMCID: PMC7566701, DOI: 10.1172/jci.insight.138815.Peer-Reviewed Original ResearchConceptsCortical bone lossBone lossControl miceAged miceCortical boneAge-associated bone lossOsteoclastogenic cytokine RANKLOsteocyte-derived RANKLTrabecular boneMonths of ageSenescent cellsConditional knockout miceHuman cell culture modelsRANKL levelsCytokine RANKLRANKL productionKnockout miceTranscription factor GATA4Cell culture modelSenolytic compoundsRANKLMiceAgeBoneCellular senescence