Bone adapts according to the mechanical environment,and this adaptation can be visualized by altering its shape,size,and microarchitecture.Bone adaptation was recognized more than a century ago,with a description pres...Bone adapts according to the mechanical environment,and this adaptation can be visualized by altering its shape,size,and microarchitecture.Bone adaptation was recognized more than a century ago,with a description presented in The Law of Bone Remodeling.Furthermore,the conceptual model of“The Mechanostat”provides a quantitative relationship between the magnitude of bone tissue deformation(strain)and bone adaptive responses.However,upon maintaining a constant strain magnitude,various bone responses were observed experimentally under different loading parameters(e.g.,frequency,rate,number of load cycles,rest insertion,and waveform).Nevertheless,the precise relationship between mechanical signals and bone adaptation remains unclear.Accordingly,we reviewed in vivo loading studies to determine the quantitative relationships between various mechanical signals and bone adaptive responses in various animal loading models.Additionally,we explored how these relationships are influenced by pathophysiological factors,such as age,sex,and estrogen deficiency.Moreover,mechanistic studies that consider cellular mechanical microenvironments to explain these quantitative relationships are discussed.A general formula that considers the bone adaptive response as a function of different loading parameters was proposed.This review may enhance our understanding of bone adaptation and offer guidance for clinicians to develop effective mechanotherapies to prevent bone loss.展开更多
Osteoblasts are derived from mesenchymal stem cells （MSCs）, which initiate and regulate bone formation. New strategies for osteoporosis treatments have aimed to control the fate of MSCs. While functional disuse decr...Osteoblasts are derived from mesenchymal stem cells （MSCs）, which initiate and regulate bone formation. New strategies for osteoporosis treatments have aimed to control the fate of MSCs. While functional disuse decreases MSC growth and osteogenic potentials, mechanical signals enhance MSC quantity and bias their differentiation toward osteoblastogenesis. Through a non-invasive dynamic hydraulic stimulation （DHS）, we have found that DHS can mitigate trabecular bone loss in a functional disuse model via rat hindlimb suspension （HLS）. To further elucidate the downstream cellular effect of DHS and its potential mechanism underlying the bone quality enhancement, a longitudinal in vivo study was designed to evaluate the MSC populations in response to DHS over 3, 7, 14, and 21 days. Five-month old female Sprague Dawley rats were divided into three groups for each time point： age-matched control, HLS, and HLS＋DHS. DHS was delivered to the right mid-tibiae with a daily ＂10 min on-5 min off-10 min on＂ loading regime for five days/week. At each sacrifice time point, bone marrow MSCs of the stimulated and control tibiae were isolated through specific cell surface markers and quantified by flow cytometry analysis. A strong time-dependent manner of bone marrow MSC induction was observed in response to DHS, which peaked on day 14. After 21 days, this effect of DHS was diminished. This study indicates that the MSC pool is positively influenced by the mechanical signals driven by DHS. Coinciding with our previous findings of mitigation of disuse bone loss, DHS induced changes in MSC number may bias the differentiation of the MSC population towards osteoblastogenesis, thereby promoting bone formation under disuse conditions. This study provides insights into the mechanism of time-sensitive MSC induction in response to mechanical loading, and for the optimal design of osteovorosis treatments.展开更多
Ultrasound imaging has been widely used in clinical diagnoses,such as B-mode and M-mode ultrasound imaging for cardiovascular,abdomen,OB-Gyn,and other soft tissue and organs in clinical diagnoses.Ultrasound imaging ha...Ultrasound imaging has been widely used in clinical diagnoses,such as B-mode and M-mode ultrasound imaging for cardiovascular,abdomen,OB-Gyn,and other soft tissue and organs in clinical diagnoses.Ultrasound imaging has traditionally been limited in its application to bone because of the high acoustic impedance and density of trabecular and cortical bone structure and density alterations,high wave reflection,absorption,scattering,and low penetration,which result in significant reflection and attenuation of ultrasonic energy in such mineral tissues.Recent advancements in quantitative ultrasound technology have opened new possibilities for noninvasive characteristics of bone quality through transmitted or backscattered signals,offering a radiation-free alternative to traditional imaging modalities like dual-energy X-ray absorptiometry(DEX),X-rays,and CT scans.In addition,low-intensity ultrasound(LIUS)has been studied and applied to promote bone regeneration and fracture healing through induced mechanotransduction in tissue and cells.The field of bone ultrasound encompasses fundamental research on the interaction of elastic waves with cortical and trabecular bone microstructures,the development of innovative imaging methodologies and medical applications such as bone health assessment for osteoporosis diagnosis,therapeutic use of LIUS,and phase aberration correction inside the skull.This work has highlighted recent developments and advancements in ultrasound diagnosis and therapeutics,induced cellular and molecular pathways,and future directions using ultrasound as a promising imaging tool and treatment method.展开更多
The use of mechanical biology and biomechanical signal transduction is a novel approach to attenuate biological tissue degeneration,whereas the understanding of specific cellular responses is critical to delineate the...The use of mechanical biology and biomechanical signal transduction is a novel approach to attenuate biological tissue degeneration,whereas the understanding of specific cellular responses is critical to delineate the underlying mechanism.Dynamic mechanical signals with optimized loading signals,i.e.,intensity and frequency,have been shown to have the potential to regulate adaptation and regeneration.Mechanotransduction pathways are of great interest in elucidating how mechanical signals produce such observed effects,including reduced tissue mass loss,increased healing and formation,and cell differentiation.While mechanobiology in the adaptation of cells and tissues is observed and recorded in the literature,its application in disease mechanism and treatment is under development.We would congratulate the opening of the Mechanobiology in Medicine journal,which provides an effective platform for advanced research in basic mechanotransduction and its translation in disease diagnosis,therapeutics,and beyond.This review aims to develop a cellular and molecular understanding of the mecha-notransduction processes in tissue regeneration,which may provide new insights into disease mechanisms and the promotion of healing.Particular attention is allotted to the responses of mechanical loading,including potential cellular and molecular pathways,such as mechanotransduction associated with mechanotransduction pathways(e.g.,Piezo ion channels and Wnt signaling),immune-response,neuron development,tissue adaptation and repair,and stem cell differentiation.Altogether,these discussed data highlight the complex yet highly coordi-nated mechanotransduction process in tissue regeneration.展开更多
基金supported by National Natural Science Foundation of China[12272017]Beijing Natural Science Foundation[L232058].
文摘Bone adapts according to the mechanical environment,and this adaptation can be visualized by altering its shape,size,and microarchitecture.Bone adaptation was recognized more than a century ago,with a description presented in The Law of Bone Remodeling.Furthermore,the conceptual model of“The Mechanostat”provides a quantitative relationship between the magnitude of bone tissue deformation(strain)and bone adaptive responses.However,upon maintaining a constant strain magnitude,various bone responses were observed experimentally under different loading parameters(e.g.,frequency,rate,number of load cycles,rest insertion,and waveform).Nevertheless,the precise relationship between mechanical signals and bone adaptation remains unclear.Accordingly,we reviewed in vivo loading studies to determine the quantitative relationships between various mechanical signals and bone adaptive responses in various animal loading models.Additionally,we explored how these relationships are influenced by pathophysiological factors,such as age,sex,and estrogen deficiency.Moreover,mechanistic studies that consider cellular mechanical microenvironments to explain these quantitative relationships are discussed.A general formula that considers the bone adaptive response as a function of different loading parameters was proposed.This review may enhance our understanding of bone adaptation and offer guidance for clinicians to develop effective mechanotherapies to prevent bone loss.
基金supported by the National Institute of Health (R01 AR52379, AR49286, and AR60621)
文摘Osteoblasts are derived from mesenchymal stem cells （MSCs）, which initiate and regulate bone formation. New strategies for osteoporosis treatments have aimed to control the fate of MSCs. While functional disuse decreases MSC growth and osteogenic potentials, mechanical signals enhance MSC quantity and bias their differentiation toward osteoblastogenesis. Through a non-invasive dynamic hydraulic stimulation （DHS）, we have found that DHS can mitigate trabecular bone loss in a functional disuse model via rat hindlimb suspension （HLS）. To further elucidate the downstream cellular effect of DHS and its potential mechanism underlying the bone quality enhancement, a longitudinal in vivo study was designed to evaluate the MSC populations in response to DHS over 3, 7, 14, and 21 days. Five-month old female Sprague Dawley rats were divided into three groups for each time point： age-matched control, HLS, and HLS＋DHS. DHS was delivered to the right mid-tibiae with a daily ＂10 min on-5 min off-10 min on＂ loading regime for five days/week. At each sacrifice time point, bone marrow MSCs of the stimulated and control tibiae were isolated through specific cell surface markers and quantified by flow cytometry analysis. A strong time-dependent manner of bone marrow MSC induction was observed in response to DHS, which peaked on day 14. After 21 days, this effect of DHS was diminished. This study indicates that the MSC pool is positively influenced by the mechanical signals driven by DHS. Coinciding with our previous findings of mitigation of disuse bone loss, DHS induced changes in MSC number may bias the differentiation of the MSC population towards osteoblastogenesis, thereby promoting bone formation under disuse conditions. This study provides insights into the mechanism of time-sensitive MSC induction in response to mechanical loading, and for the optimal design of osteovorosis treatments.
基金supported by NIH R01 AR061821 and R01 AR052379,and NSF#2327144.
文摘Ultrasound imaging has been widely used in clinical diagnoses,such as B-mode and M-mode ultrasound imaging for cardiovascular,abdomen,OB-Gyn,and other soft tissue and organs in clinical diagnoses.Ultrasound imaging has traditionally been limited in its application to bone because of the high acoustic impedance and density of trabecular and cortical bone structure and density alterations,high wave reflection,absorption,scattering,and low penetration,which result in significant reflection and attenuation of ultrasonic energy in such mineral tissues.Recent advancements in quantitative ultrasound technology have opened new possibilities for noninvasive characteristics of bone quality through transmitted or backscattered signals,offering a radiation-free alternative to traditional imaging modalities like dual-energy X-ray absorptiometry(DEX),X-rays,and CT scans.In addition,low-intensity ultrasound(LIUS)has been studied and applied to promote bone regeneration and fracture healing through induced mechanotransduction in tissue and cells.The field of bone ultrasound encompasses fundamental research on the interaction of elastic waves with cortical and trabecular bone microstructures,the development of innovative imaging methodologies and medical applications such as bone health assessment for osteoporosis diagnosis,therapeutic use of LIUS,and phase aberration correction inside the skull.This work has highlighted recent developments and advancements in ultrasound diagnosis and therapeutics,induced cellular and molecular pathways,and future directions using ultrasound as a promising imaging tool and treatment method.
文摘The use of mechanical biology and biomechanical signal transduction is a novel approach to attenuate biological tissue degeneration,whereas the understanding of specific cellular responses is critical to delineate the underlying mechanism.Dynamic mechanical signals with optimized loading signals,i.e.,intensity and frequency,have been shown to have the potential to regulate adaptation and regeneration.Mechanotransduction pathways are of great interest in elucidating how mechanical signals produce such observed effects,including reduced tissue mass loss,increased healing and formation,and cell differentiation.While mechanobiology in the adaptation of cells and tissues is observed and recorded in the literature,its application in disease mechanism and treatment is under development.We would congratulate the opening of the Mechanobiology in Medicine journal,which provides an effective platform for advanced research in basic mechanotransduction and its translation in disease diagnosis,therapeutics,and beyond.This review aims to develop a cellular and molecular understanding of the mecha-notransduction processes in tissue regeneration,which may provide new insights into disease mechanisms and the promotion of healing.Particular attention is allotted to the responses of mechanical loading,including potential cellular and molecular pathways,such as mechanotransduction associated with mechanotransduction pathways(e.g.,Piezo ion channels and Wnt signaling),immune-response,neuron development,tissue adaptation and repair,and stem cell differentiation.Altogether,these discussed data highlight the complex yet highly coordi-nated mechanotransduction process in tissue regeneration.
