Joint loading-driven bone formation and signaling pathways predicted from genome-wide expression profiles

Zhang, Ping; Turner, Charles H.; Yokota, Hiroki

doi:10.1016/j.bone.2009.01.367

Cited by 46 publications

(47 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both CRLF1 and CLCF1 mRNA levels in osteoblasts are stimulated by parathyroid hormone [49], an agent that stimulates bone formation when used therapeutically, and that has been shown to be dependent on gp130 signalling within the osteoblast lineage to have this effect [50]. Surprisingly however, upregulation of CLCF1 and CRLF1 is not generalizable to all activities that stimulate bone formation, since CLCF1 and CRLF mRNA levels are lowered in bones subjected to mechanical loading [51].…”

Section: Effects Of Clcf1 and Crlf1 Composite Cytokines On The Neuralmentioning

confidence: 96%

Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders

Sims

2015

Cytokine & Growth Factor Reviews

View full text Add to dashboard Cite

Section: Effects Of Clcf1 and Crlf1 Composite Cytokines On The Neuralmentioning

confidence: 96%

Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders

Sims

2015

Cytokine & Growth Factor Reviews

View full text Add to dashboard Cite

“…The load-driven pressure may generate fluid flow in a lacuna canalicular network in bone cortex. The pressure also activates bone metabolism-related genes in femur and tibia [18, 19]. In our previous works, knee loading stimulated bone formation by conducting bone histomorphometry using the cross-sections at 25% (distal femur), 50% (midshaft), and 75% (proximal femur) of the length of the femur from the loading site.…”

Section: Introductionmentioning

confidence: 99%

Knee loading protects against osteonecrosis of the femoral head by enhancing vessel remodeling and bone healing

Liu

et al. 2015

Bone

Self Cite

View full text Add to dashboard Cite

Osteonecrosis of the femoral head is a serious orthopedic problem. Moderate loads with knee loading promote bone formation, but its 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 significant induced bone loss, and knee loading stimulated both vessel remodeling and bone healing. The osteonecrosis group exhibited the lowest trabecular BV/TV (p < 0.001) in the femoral head, and lowest femoral BMD and BMC (both p < 0.01). However, knee loading increased trabecular BV/TV (p < 0.05) as well as BMD and BMC (both p < 0.05). Osteonecrosis decreased the vessel volume, vessel number and VEGF expression (all p < 0.01), and knee loading increased them (all p < 0.01). Osteonecrosis activated osteoclast development, and knee loading reduced its formation, migration, adhesion and the level of “pit” formation (all p < 0.001). Furthermore, knee loading significantly increased osteoblast differentiation and CFU-F (both p < 0.001). A significant positive correlation was observed between vessel remodeling and bone healing (both p < 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.

show abstract

“…Dynamic deformations of the epiphysis cause alterations in fluid pressure in the intramedullary cavity, driving oscillatory fluid flow and molecular transport in the lacunocanalicular network in the bone matrix and in the medullary cavity [4][5][6]. Fluid flow may cause shear stress to osteocytes, stimulating a Wnt-signaling pathway, leading to osteoblast differentiation and the initiation of bone formation [7]. The results from animal studies demonstrate the potential therapeutic effects of knee loading in diseases of low bone mass, in cases of disuse, and in bone fracture treatment.…”

Section: Introductionmentioning

confidence: 99%

Development of a Portable Knee Rehabilitation Device That Uses Mechanical Loading

Fitzwater¹,

Dodge²,

Chien³

et al. 2013

J. Med. Devices

Self Cite

View full text Add to dashboard Cite

Joint loading is a recently developed mechanical modality, which potentially provides a therapeutic regimen to activate bone formation and prevent degradation of joint tissues. To our knowledge, however, few joint loading devices are available for clinical or pointof-care applications. Using a voice-coil actuator, we developed an electromechanical loading system appropriate for human studies and preclinical trials that should prove both safe and effective. Two specific tasks for this loading system were development of loading conditions (magnitude and frequency) suitable for humans, and provision of a convenient and portable joint loading apparatus. Desktop devices have been previously designed to evaluate the effects of various loading conditions using small and large animals. However, a portable knee loading device is more desirable from a usability point of view. In this paper, we present such a device that is designed to be portable, providing a compact, user-friendly loader. The portable device was employed to evaluate its capabilities using a human knee model. The portable device was characterized for force-pulse width modulation duty cycle and loading frequency properties. The results demonstrate that the device is capable of producing the necessary magnitude of forces at appropriate frequencies to promote the stimulation of bone growth and which can be used in clinical studies for further evaluations.

show abstract

Joint loading-driven bone formation and signaling pathways predicted from genome-wide expression profiles

Cited by 46 publications

References 48 publications

Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders

Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders

Knee loading protects against osteonecrosis of the femoral head by enhancing vessel remodeling and bone healing

Development of a Portable Knee Rehabilitation Device That Uses Mechanical Loading

Contact Info

Product

Resources

About