title: Knee loading inhibits osteoclast lineage in a mouse model of osteoarthritis.
abstract: Osteoarthritis (OA) is a whole joint disorder that involves cartilage degradation and periarticular bone response. Changes of cartilage and subchondral bone are associated with development and activity of osteoclasts from subchondral bone. Knee loading promotes bone formation, but its effects on OA have not been well investigated. Here, we hypothesized that knee loading regulates subchondral bone remodeling by suppressing osteoclast development, and prevents degradation of cartilage through crosstalk of bone-cartilage in osteoarthritic mice. Surgery-induced mouse model of OA was used. Two weeks application of daily dynamic knee loading significantly reduced OARSI scores and CC/TAC (calcified cartilage to total articular cartilage), but increased SBP (subchondral bone plate) and B.Ar/T.Ar (trabecular bone area to total tissue area). Bone resorption of osteoclasts from subchondral bone and the differentiation of osteoclasts from bone marrow-derived cells were completely suppressed by knee loading. The osteoclast activity was positively correlated with OARSI scores and negatively correlated with SBP and B.Ar/T.Ar. Furthermore, knee loading exerted protective effects by suppressing osteoclastogenesis through Wnt signaling. Overall, osteoclast lineage is the hyper responsiveness of knee loading in osteoarthritic mice. Mechanical stimulation prevents OA-induced cartilage degeneration through crosstalk with subchondral bone. Knee loading might be a new potential therapy for osteoarthritis patients.
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xinle
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.|Department of Pharmacology, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin 300100, China.
authors.forename: Daquan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Kaijun
authors.initials: K
authors.lastname: Niu
authors.affiliation: Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, IN 46202, USA.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokota
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.|Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, IN 46202, USA.|TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Tianjin 300457, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000473:pathology* / Q000503:physiopathology; D002356:Cartilage / Q000473:pathology / Q000503:physiopathology; D019070:Cell Lineage; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D020370:Osteoarthritis, Knee / Q000473:pathology* / Q000503:physiopathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D013314:Stress, Mechanical; D016474:Weight-Bearing; D060449:Wnt Signaling Pathway