Mechanical stimulation of soft tissue cells regulates osteoblast differentiation and activity through soluble factors

Osteoporosis is a disease of low bone mass that places individuals at enhanced risk for fracture, disability, and death. Hospitalizations for osteoporotic fractures exceeds those for heart attack, stroke, and breast cancer combined, and osteoporosis rates are expected to rise significantly in the coming decades. Despite this, there are limited pharmacological treatment options for osteoporosis, particularly for long-term management of this chronic condition, and the drug development pipeline is relatively bereft of new strategies and drug candidates. Consequently, there is an urgent need for new therapeutic strategies for treating osteoporosis. Here, we present a novel line of investigation examining the ability of non-invasive soft tissue manipulation (STM) to exert anabolic effects on the skeleton that may provide therapeutic benefit for individuals with low bone mass. Our rationale is premised on work showing that STM leads to decreased levels of chemokines and pro-inflammatory cytokines (such as Interleukin (IL)-1-alpha, IL-6, IL-8 and CXCL5) known to restrict the differentiation and/or activity of bone-forming osteoblasts. Additionally, STM is associated with increased serum levels of the bone formation marker N-terminal propeptide of type 1 procollagen and decreased serum levels of the bone resorption marker collagen type 1 C-telopeptide in young, healthy women and increased serum P1NP levels in some women with osteoporosis. To advance this work, we hypothesized that STM promotes the differentiation and/or activity of bone-forming osteoblasts and increases bone mass. Consistent with this, we show that conditioned media from primary dermal fibroblasts subjected to STM-like stimulation is bioactive and promotes a) increased osteoprogenitor cell proliferation and differentiation in vitro and b) increased bone formation in an ex vivo bone explant model using neonatal tibiae. Consistent with this, conditioned media from primary skeletal muscle myocyte and satellite cell cultures after STM-like stimulation promotes increased osteoprogenitor cell proliferation in vitro. Collectively, these data support the idea that STM stimulation of soft tissue cells may influence skeletal homeostasis. The experimental application of STM to improving bone mass is novel in its focus, which is significant given the relationship between low bone mass and high fracture risk in patients with osteoporosis and the need for new treatment strategies for this disease.

Creator

• Hum, Julia
• Hiland, Taylor
• Anloague, Aric
• Melchior, Ross
• Lowery, Jonathan
• Delgado-Calle, Jesus

Language

• English

Palabra Clave

• osteoblast differentiation and activity
• Osteoporosis
• Soft Tissue Manipulation
• soluble factors
• Mechanical stimulation

Date created

• 2021

Related URL

• Audio presentation:  https://marian.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=b53378fc-68e1-41ee-87a7-adf70123a2f0

Resource type

• Poster

Rights statement

• http://rightsstatements.org/vocab/InC/1.0/