title: Knee loading protects against osteonecrosis of the femoral head by enhancing vessel remodeling and bone healing.
abstract: Osteonecrosis of the femoral head is a serious orthopedic problem. Moderate loads with knee loading promote bone formation, but their effects on osteonecrosis have not been investigated. Using a rat model, we examined a hypothesis that knee loading enhances vessel remodeling and bone healing through the modulation of the fate of bone marrow-derived cells. In this study, osteonecrosis was induced by transecting the ligamentum teres followed by a tight ligature around the femoral neck. For knee loading, 5 N loads were laterally applied to the knee at 15 Hz for 5 min/day for 5 weeks. Changes in bone mineral density (BMD) and bone mineral content (BMC) of the femur were measured by pDEXA, and ink infusion was performed to evaluate vessel remodeling. Femoral heads were harvested for histomorphometry, and bone marrow-derived cells were isolated to examine osteoclast development and osteoblast differentiation. The results showed that osteonecrosis significantly induced bone loss, and knee loading stimulated both vessel remodeling and bone healing. The osteonecrosis group exhibited the lowest trabecular BV/TV (p b 0.001) in the femoral head, and lowest femoral BMD and BMC (both p b 0.01). However, knee loading increased trabecular BV/TV (p b 0.05) as well as BMD (pb 0.05) and BMC (p b 0.01). Osteonecrosis decreased the vessel volume (pb 0.001), vessel number (pb 0.001) and VEGF expression (p b 0.01), and knee loading increased them (pb 0.001, pb 0.001 and p b 0.01). Osteonecrosis activated osteoclast development, and knee loading reduced its formation, migration, adhesion and the level of “pit” formation (pb 0.001, pb 0.01, pb 0.001 and pb 0.001). Furthermore, knee loading significantly increased osteoblast differentiation and CFU-F (both p b 0.001). A significantly positive correlation was observed between vessel remodeling and bone healing (both p b 0.01). These results indicate that knee loading could be effective in repair osteonecrosis of the femoral head in a rat model. This effect might be attributed to promoting vessel remodeling, suppressing osteoclast development, and increasing osteoblast and fibroblast differentiation. In summary, the current study suggests that knee loading might potentially be employed as a non-invasive therapy for osteonecrosis of the femoral head.
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: 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: Jie
authors.initials: J
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 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. Electronic address: pizhang2008@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001854:Bone Marrow Cells / Q000473:pathology / Q000502:physiology; D016723:Bone Remodeling; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D005270:Femur Head / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D005271:Femur Head Necrosis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D010006:Osteoblasts / Q000473:pathology / Q000502:physiology; D010010:Osteoclasts / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D066253:Vascular Remodeling; D016474:Weight-Bearing / Q000502:physiology*
keywords: Bone remodeling; Knee loading; Osteoblast; Osteoclast; Osteonecrosis; Vessel remodeling