title: Aberrant Activation of TGF-β in Subchondral Bone at the Onset of Rheumatoid Arthritis Joint Destruction.
abstract: Rheumatoid arthritis (RA) is an autoimmune disease that often leads to joint destruction. A myriad of drugs targeting the immune abnormalities and downstream inflammatory cascades have been developed, but the joint destruction is not effectively halted. Here we report that aberrant activation of TGF-β in the subchondral bone marrow by immune response increases osteoprogenitors and uncoupled bone resorption and formation in RA mouse/rat models. Importantly, either systemic or local blockade of TGF-β activity in the subchondral bone attenuated articular cartilage degeneration in RA. Moreover, conditional deletion of TGF-β receptor II (Tgfbr2) in nestin-positive cells also effectively halted progression of RA joint destruction. Our data demonstrate that aberrant activation of TGF-β in the subchondral bone is involved at the onset of RA joint cartilage degeneration. Thus, modulation of subchondral bone TGF-β activity could be a potential therapy for RA joint destruction.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, PR China.|Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, PR China.|Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Liwei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Institute of Spine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Bian
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, PR China.|Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Orthopaedics and Traumatology, Faculty of Medicine, The University of Hong Kong, Hong Kong, PR China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Gehua
authors.initials: G
authors.lastname: Zhen
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Crane
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, PR China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D001862:Bone Resorption / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D003094:Collagen; D004195:Disease Models, Animal; D007596:Joints / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064231:Nestin / Q000378:metabolism; D009500:Neutralization Tests; D010012:Osteogenesis; D011917:Rats, Inbred Lew; D015398:Signal Transduction; D013977:Tibia / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D064231:Nestin; D016212:Transforming Growth Factor beta; D003094:Collagen
keywords: CARTILAGE DEGENERATION; MESENCHYMAL STEM CELLS; RHEUMATOID ARTHRITIS; SUBCHONDRAL BONE; TGF-β