Loss and rescue of osteocalcin and osteopontin modulate osteogenic and angiogenic features of mesenchymal stem/stromal cells.

Noncollagenous proteins in the bone extracellular matrix, such as osteocalcin (OC) and osteopontin (OPN), inherent to evolution of bone as a skeletal tissue, are known to regulate bone formation and mineralization. However, the fundamental basis of this regulatory role remains unknown. Here, for the first time, we use mouse mesenchymal stem/stromal cells (MSC) lacking both OC and OPN to investigate the mechanistic roles of OC and OPN on the proliferation capacity and differentiation ability of MSC. We found that the loss of OC and OPN reduces stem cells self-renewal potential and multipotency, affects their differentiation into an osteogenic lineage, and impairs their angiogenic potential while maintaining chondrogenic and adipogenic lineages. Moreover, loss of OC and OPN compromises the extracellular matrix integrity and maturation, observed by an unexpected enhancement of glycosaminoglycans content that are associated with a more primitive skeletal connective tissue, and by a delay on the maturation of mineral species produced. Interestingly, exogenously supplemented OC and OPN were able to rescue MSC proliferative and osteogenic potential along with matrix integrity and mineral quality. Taken together, these results highlight the key contributions of OC and OPN in enhancing osteogenesis and angiogenesis over primitive connective tissue, and support a potential therapeutic approach based on their exogenous supplementation.

Acute effects of foam rolling on passive stiffness, stretch sensation and fascial sliding: A randomized controlled trial.

PURPOSE: Foam Rolling (FR), aims to mimic the effects of manual therapy and tackle dysfunctions of the skeletal muscle and connective tissue. It has been shown to induce improvements in flexibility, but the underlying mechanisms are poorly understood. The aim of the present study was to further elucidate the acute, systemic and tissue-specific responses evoked by FR. METHODS: In a crossover study, 16 (34 ±â€¯6y, 6f) participants received all of the following interventions in a random order: a) 2 × 60 seconds of FR at the anterior thigh, b) 2 × 60 seconds of passive static stretching of the anterior thigh (SS), and c) no intervention (CON). Maximal active and passive knee flexion range of motion (ROM), passive stiffness, sliding of fascial layers, as well as knee flexion angle of first subjectively perceived stretch sensation (FSS) were evaluated before and directly after each intervention. RESULTS: Flexibility increased only after, FR (active (+1.8 ±â€¯1.9%) and passive ROM (+3.4 ±â€¯2.7%), p = .006, respectively) and SS (passive ROM (+3.2 ±â€¯3.5%), p = .002). Angle of FSS was altered following FR (+4.3° (95% CI: 1.4°-7.2°)) and SS (+6.7° (3.7°-9.6°)), while tissue stiffness remained unchanged after any intervention compared to baseline. Movement of the deepest layer (-5.7 mm (-11.3 mm to -0.1 mm)) as well as intrafascial sliding between deep and superficial layer (-4.9 mm (-9.mm to -0.7 mm)) decreased only after FR. CONCLUSION: FR improved knee flexion ROM without altering passive stiffness, but modified the perception of stretch as well as the mobility of the deep layer of the fascia lata. The mechanisms leading to altered fascial sliding merit further investigation.

Improving the New Definition of Fascial System.

BACKGROUND/AIMS: Bone tissue is defined as connective tissue with an embryological derivation that reflects the origin of the fascial system. The surface of the bone tissue makes the bone system the largest organ in the human body, whose most representative cells are the osteocytes. It is essential for the general health of the individual, influencing different organs and systems, through the hormonal paracrine production of the osteocytes. In the modern scientific panorama, bone tissue has been included in the definition of fascial continuum only in one of our articles. The intent of this article is to enrich the motivations that led to the introduction of the bone in the fascia description, illustrating its local and systemic properties. The final theme of the current text will be to give a definition of the fascial system more congruent with modern scientific notions. METHODS: The article collects the embryological and anatomical information on bone and exposes the most recent information in a narrative review. RESULTS: The results of the literature show that bone is specialized connective tissue. CONCLUSION: Bone tissue must be included in the definitions of what is considered fascial tissue, so as to have a better view of the fascial system.

Acute Effects of Connective Tissue Manipulation on Autonomic Function in Healthy Young Women.

BACKGROUND: Connective tissue manipulation (CTM) has therapeutic effects on diseases with autonomic imbalance, yet its mechanisms of action are not clearly identified. OBJECTIVE: The aim of this study was to investigate acute autonomic responses to CTM in healthy young women with various physical activity levels. METHOD: The study was designed as a nonrandomized, controlled single-center study. Healthy women aged between 18 and 25 years were assigned to a connective tissue manipulation group (CTMG) (n = 150) or a control group (CG) (n = 60). CTM was applied to the CTMG while the CG did not receive any intervention. Respiratory rate (RR), heart rate, systolic/diastolic blood pressures (SP/DP), oxygen saturation (OS) and body temperature were measured. The International Physical Activity Questionnaire short form was used to determine physical activity levels. -Results: Analysis revealed significant reduction in SP and DP and an increment in RR in the CTMG (p < 0.05). RR increased and SP decreased among inactive, SP decreased among moderately active, and SP and OS decreased among highly active participants in the CTMG (p < 0.05). There were no significant alterations in the CG (p > 0.05). CONCLUSIONS: CTM has an immediate reducing effect on sympathetic activity in healthy young women independently from the physical activity level. Future studies are needed to clarify long-term effects of CTM on autonomic functions in healthy individuals.

Understanding Qi Running in the Meridians as Interstitial Fluid Flowing via Interstitial Space of Low Hydraulic Resistance.

Qi, blood and the meridians are fundamental concepts in Chinese medicine (CM), which are components of the human body and maintain physiological function. Pathological changes of qi, blood and meridians may lead to discomfort and disease. Treatment with acupuncture or herbal medicine aims to regulate qi and blood so as to recover normal function of the meridians. This paper explores the nature of qi as well as compares and correlates them with the structures of the human body. We propose a conceptualization of qi as being similar to the interstitial fluid, and the meridians as being similar to interstitial space of low hydraulic resistance in the body. Hence, qi running in the meridians can be understood as interstitial fluid flowing via interstitial space of low hydraulic resistance.

Defining the fascial system.

Fascia is a widely used yet indistinctly defined anatomical term that is concurrently applied to the description of soft collagenous connective tissue, distinct sections of membranous tissue, and a body pervading soft connective tissue system. Inconsistent use of this term is causing concern due to its potential to confuse technical communication about fascia in global, multiple discipline- and multiple profession-spanning discourse environments. The Fascia Research Society acted to address this issue by establishing a Fascia Nomenclature Committee (FNC) whose purpose was to clarify the terminology relating to fascia. This committee has since developed and defined the terms a fascia, and, more recently, the fascial system. This article reports on the FNC's proposed definition of the fascial system.

Analysis of specific absorption rate and internal electric field in human biological tissues surrounding an air-core coil-type transcutaneous energy transmission transformer.

In this study, we analyzed the internal electric field E and specific absorption rate (SAR) of human biological tissues surrounding an air-core coil transcutaneous energy transmission transformer. Using an electromagnetic simulator, we created a model of human biological tissues consisting of a dry skin, wet skin, fat, muscle, and cortical bone. A primary coil was placed on the surface of the skin, and a secondary coil was located subcutaneously inside the body. The E and SAR values for the model representing a 34-year-old male subject were analyzed using electrical frequencies of 0.3-1.5 MHz. The transmitting power was 15 W, and the load resistance was 38.4 Ω. The results showed that the E values were below the International Commission on Non-ionizing Radiation Protection (ICNIRP) limit for the general public exposure between the frequencies of 0.9 and 1.5 MHz, and SAR values were well below the limit prescribed by the ICNIRP for the general public exposure between the frequencies of 0.3 and 1.2 MHz.

Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology.

Complementary and integrative treatments, such as massage, acupuncture, and yoga, are used by increasing numbers of cancer patients to manage symptoms and improve their quality of life. In addition, such treatments may have other important and currently overlooked benefits by reducing tissue stiffness and improving mobility. Recent advances in cancer biology are underscoring the importance of connective tissue in the local tumor environment. Inflammation and fibrosis are well-recognized contributors to cancer, and connective tissue stiffness is emerging as a driving factor in tumor growth. Physical-based therapies have been shown to reduce connective tissue inflammation and fibrosis and thus may have direct beneficial effects on cancer spreading and metastasis. Meanwhile, there is currently little knowledge on potential risks of applying mechanical forces in the vicinity of tumors. Thus, both basic and clinical research are needed to understand the full impact of integrative oncology on cancer biology as well as whole person health. Cancer Res; 76(21); 6159-62. ©2016 AACR.

Therapeutic effects of connective tissue manipulation on wound healing and bacterial colonization count among patients with diabetic foot ulcer.

This study investigated the therapeutic effects of connective tissue manipulation (CTM) in diabetic foot ulcer (DFU). A total of 20 participants (10 in CTM group and 10 in conventional treatment group (CG)) with DFU underwent the conventional DFU treatment. In addition, the CTM group received CTM twice per week for 6 weeks. The percentage wound area reduction (PWAR) and bacterial colonization count (BCC) in log10 colony-forming units (CFU) per ml wound fluid was evaluated at baseline and six weeks. Results showed a significant change in PWAR in CTM (p < 0.05, t = 3.82, Df = 9, CI L = 0.98 U = 3.81) and CG (p < 0.05, t = 2.97, Df = 9,CI L = 0.26 U = 1.98). Mean reduction of BCC showed a significant reduction (p < 0.05), with percentage of BCC reduction higher in CTM group (6.45%) than CG (3.55%). The findings suggest CTM as an effective adjunct therapy for DFU to enhance conventional treatments.

Investigation of the effects of connective tissue mobilisation on quality of life and emotional status in healthy subjects.

BACKGROUND: Connective Tissue Massage (CTM) or Manipulation is a bodywork technique which lies at the interface between alternative approaches. The autonomic balancing responses to CTM can be useful in the treatment of anxiety. AIM: This study was planned to investigate the effects of connective tissue mobilization (CTM) on quality of life and emotional status in healthy subjects. Design; Prospective trial, Setting; Treatment and Population. The study was conducted on 100 volunteers (students). Students in second class were in CTM group (20,49±1,37 years) and students (19,50±1,15 years) educating in class 1 were in control group. METHODS: Participants were assessed before and after CTM according to flexibility of trunk flexion, hamstring muscles, trunk hyperextension and lateral flexion. It was used The SF-36 Health-Related Quality of Life Inventory (SF-36) to assess general health status and Beck Depression Scale was used for assessing emotional status. RESULTS: It was observed a significant increase at lateral flexion to the right of trunk (p=0,03) in CTM group after application. It was found a significant difference (p=0,009) in emotional status between groups. It was found differences at general health level (p=0,001), limitations in emotional role (p=0,016) in SF-36. It was some differences in depression status and some subscales of SF-36 (general health, social status, emotional well-being, pain and energy levels) in favour of control group before application. It was no difference between groups after application. CONCLUSION: CTM could be used for minimizing depressive symptoms, improving quality of life in healthy young subjects.

Thermal-mechanical deformation modelling of soft tissues for thermal ablation.

Modeling of thermal-induced mechanical behaviors of soft tissues is of great importance for thermal ablation. This paper presents a method by integrating the heating process with thermal-induced mechanical deformations of soft tissues for simulation and analysis of the thermal ablation process. This method combines bio-heat transfer theories, constitutive elastic material law under thermal loads as well as non-rigid motion dynamics to predict and analyze thermal-mechanical deformations of soft tissues. The 3D governing equations of thermal-mechanical soft tissue deformation are discretized by using the finite difference scheme and are subsequently solved by numerical algorithms. Experimental results show that the proposed method can effectively predict the thermal-induced mechanical behaviors of soft tissues, and can be used for the thermal ablation therapy to effectively control the delivered heat energy for cancer treatment.

Acupuncture, connective tissue, and peripheral sensory modulation.

Although considerable controversy surrounds the legitimacy of acupuncture as a treatment, a growing literature on the physiological effects of acupuncture needling in animals and humans is providing new insights into basic cellular mechanisms including connective tissue mechanotransduction and purinergic signaling. This review summarizes these findings and proposes a model combining connective tissue plasticity and peripheral sensory modulation in response to the sustained stretching of tissue that results from acupuncture needle manipulation.

Anisotropic tissue motion induced by acupuncture needling along intermuscular connective tissue planes.

OBJECTIVES: Acupuncture needle manipulation causes mechanical deformation of connective tissue, which in turn results in mechanical stimulation of fibroblasts, with active changes in cell shape and autocrine purinergic signaling. We have previously shown using ultrasound elastography in humans that acupuncture needle manipulation causes measurable movement of tissue up to several centimeters away from the needle. The goal of this study was to quantify the spatial pattern of tissue displacement and deformation (shear strain) in response to acupuncture needling along an intermuscular connective tissue plane compared with needling over the belly of a muscle. DESIGN: Eleven (11) healthy human subjects underwent a single testing session during which robotic acupuncture needling was performed while recording tissue displacement using ultrasound. Outcome measures were axial and lateral tissue displacement as well as lateral shear strain calculated using ultrasound elastography postprocessing. RESULTS: Tissue displacement and strain extended further in the longitudinal direction when needling between muscles, and in the transverse direction when needling over the belly of a muscle. CONCLUSIONS: The anisotropic tissue motion observed in this study may influence the spatial distribution of local connective tissue cellular responses following acupuncture needle manipulation.

Training principles for fascial connective tissues: scientific foundation and suggested practical applications.

Conventional sports training emphasizes adequate training of muscle fibres, of cardiovascular conditioning and/or neuromuscular coordination. Most sports-associated overload injuries however occur within elements of the body wide fascial net, which are then loaded beyond their prepared capacity. This tensional network of fibrous tissues includes dense sheets such as muscle envelopes, aponeuroses, as well as specific local adaptations, such as ligaments or tendons. Fibroblasts continually but slowly adapt the morphology of these tissues to repeatedly applied challenging loading stimulations. Principles of a fascia oriented training approach are introduced. These include utilization of elastic recoil, preparatory counter movement, slow and dynamic stretching, as well as rehydration practices and proprioceptive refinement. Such training should be practiced once or twice a week in order to yield in a more resilient fascial body suit within a time frame of 6-24 months. Some practical examples of fascia oriented exercises are presented.

Strain hardening of fascia: static stretching of dense fibrous connective tissues can induce a temporary stiffness increase accompanied by enhanced matrix hydration.

This study examined a potential cellular basis for strain hardening of fascial tissues: an increase in stiffness induced by stretch and subsequent rest. Mice lumbodorsal fascia were isometrically stretched for 15 min followed by 30 min rest (n=16). An increase in stiffness was observed in the majority of samples, including the nonviable control samples. Investigations with porcine lumbar fascia explored hydration changes as an explanation (n=24). Subject to similar loading procedures, tissues showed decreases in fluid content immediately post-stretch and increases during rest phases. When allowed sufficient resting time, a super-compensation phenomenon was observed, characterised by matrix hydration higher than initial levels and increases in tissue stiffness. Therefore, fascial strain hardening does not seem to rely on cellular contraction, but rather on this super-compensation. Given a comparable occurrence of this behaviour in vivo, clinical application of routines for injury prevention merit exploration.

Pandiculation: nature's way of maintaining the functional integrity of the myofascial system?

Pandiculation is the involuntary stretching of the soft tissues, which occurs in most animal species and is associated with transitions between cyclic biological behaviors, especially the sleep-wake rhythm (Walusinski, 2006). Yawning is considered a special case of pandiculation that affects the musculature of the mouth, respiratory system and upper spine (Baenninger, 1997). When, as often happens, yawning occurs simultaneously with pandiculation in other body regions (Bertolini and Gessa, 1981; Lehmann, 1979; Urba-Holmgren et al., 1977) the combined behavior is referred to as the stretch-yawning syndrome (SYS). SYS has been associated with the arousal function, as it seems to reset the central nervous system to the waking state after a period of sleep and prepare the animal to respond to environmental stimuli (Walusinski, 2006). This paper explores the hypothesis that the SYS might also have an auto-regulatory role regarding the locomotor system: to maintain the animal's ability to express coordinated and integrated movement by regularly restoring and resetting the structural and functional equilibrium of the myofascial system. It is now recognized that the myofascial system is integrative, linking body parts, as the force of a muscle is transmitted via the fascial structures well beyond the tendonous attachments of the muscle itself (Huijing and Jaspers, 2005). It is argued here that pandiculation might preserve the integrative role of the myofascial system by (a) developing and maintaining appropriate physiological fascial interconnections and (b) modulating the pre-stress state of the myofascial system by regularly activating the tonic musculature. The ideas presented here initially arose from clinical observations during the practice of a manual therapy called Muscular Repositioning (MR) (Bertolucci, 2008; Bertolucci and Kozasa, 2010a; Bertolucci, 2010b). These observations were supplemented by a review of the literature on the subject. A possible link between MR and SYS is presented: The neural reflexes characteristically evoked through MR are reminiscent of SYS, which both suggests that MR might stimulate parts of the SYS reaction, and also points to one of MR's possible mechanisms of action.

A generalized haptic feedback approach for arbitrarily shaped objects.

In surgery procedures, haptic interaction provides surgeons with indispensable information to accurately locate the surgery target. This is especially critical when visual feedback cannot provide sufficient information and tactile interrogation, such as palpating some region of tissue, is required to locate a specific underlying tumor. However, in most current surgery simulators, the haptic interaction model is usually simplified into a contact sphere or rod model, leaving arbitrarily shaped intersection haptic feedback between target tissue and surgery instrument less unreliable. In this paper, a novel haptic feedback algorithm is introduced for generating the feedback forces in surgery simulations. The proposed algorithm initially employs three Layered Depth Images (LDI) to sample the 3D objects in X, Y and Z directions. A secondary analysis scans through two sampled meshes and detects their penetration volume. Based on the principle that interaction force should minimize the penetration volume, the haptic feedback force is derived directly. Additionally, a post-processing technique is developed to render distinct physical tissue properties across different interaction areas. The proposed approach does not require any pre-processing and is applicable for both rigid and deformable objects.

Glaucomatous cupping of the lamina cribrosa: a review of the evidence for active progressive remodeling as a mechanism.

The purpose of this review is to examine the literature in an attempt to elucidate a biomechanical basis for glaucomatous cupping. In particular, this work focuses on the role of biomechanics in driving connective tissue remodeling in the progression of laminar morphology from a normal state to that of an excavated glaucomatous state. While there are multiple contributing factors to the pathogenesis of glaucoma, we focus on laminar extracellular matrix (ECM) remodeling in glaucoma and the feedback mechanisms and signals that may guide progressive laminar cupping. We review the literature on the potential mechanisms of glaucomatous changes in the laminar ECM at the anatomic, structural, cellular and subcellular levels in the context of the biomechanical paradigm of glaucomatous onset and progression. Several conclusions can be drawn from this review. First, extensive remodeling of the lamina cribrosa ECM occurs in primary open angle glaucoma. Second, there is surprisingly little evidence to support acute mechanical damage to the lamina as the principal mechanism of cupping. Third, ONH astrocytes and lamina cribrosa cells can sense their mechanical environment and respond to mechanical stimuli by remodeling the ECM. Fourth, there is evidence suggesting that chronic remodeling of the lamina results in a progressive posterior migration of the laminar insertion into the canal wall, which eventually results in the posterior lamina inserting into the pia mater. Finally, modeling studies suggest that laminar remodeling may be a biomechanical feedback mechanism through which cells modify their environment in an attempt to return to a homeostatic mechanical environment. It is plausible that biomechanics-driven connective tissue remodeling is a mechanism in the progression of laminar morphology from a normal state to that of a cupped, excavated glaucomatous state.

Human ultraweak photon emission and the yin yang concept of Chinese medicine.

The relationship between connective tissue and meridian function is discussed in terms of energy transmission. The network of hydrogen-bonded water molecules interspersed within the collagen fibrillar matrix is especially significant for both the sensitivity of connective tissue to weak signals of mechanical pressure, heat, or electricity and the electrical intercommunication that may correlate with the meridian acupuncture system. Special electromagnetic properties of connective tissue have similar collective properties of ultraweak photon emission. A relationship between ultraweak photon emission and yin yang dynamics is based on three types of ultraweak photon emission studies, focusing on diurnal and annual dynamics, diseased states, and acupuncture points. A novel concept explains the functional (health) integrity of physiologic systems in relation to the left-right balance in ultraweak photon emission by pointing to, (1) balanced corticoneuromusculoskeletal activities and triboluminescent aspects of ultraweak photon emission by skeletal structures, and (2) local fine-tuning in oxygen supply and the formation of radical oxygen species. This approach offers testable hypotheses for further validation utilizing a combination of human photon recording techniques and specialized metabolomics for the estimation of organ-specific oxidative states.