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The “motor unit” or the “muscle” has long been considered the quantal element in the control of movement. However, in recent years new research has proved the strong interaction between muscle fibers and intramuscular connective tissue, and between muscles and fasciae, suggesting that the muscles can no longer be considered the only elements that organize movement. In addition, innervation and vascularization of muscle is strongly connected with intramuscular connective tissue. This awareness induced Luigi Stecco, in 2002, to create a new term, the “myofascial unit”, to describe the bilateral dependent relationship, both anatomical and functional, that occurs between fascia, muscle and accessory elements. The aim of this narrative review is to understand the scientific support for this new term, and whether it is actually correct to consider the myofascial unit the physiological basic element for peripheral motor control.

BACKGROUND In last years the role of fascia in proprioception and pain has been confirmed in numerous papers, but the real structure of fasciae is not still entirely known. To date, many studies have evaluated the elastic fibres in arteries, ligaments, lungs, epidermis and dermis, but only two studies exist about the elastic fibres in the fasciae, and they did not distinguish between superficial (in the subcutaneous tissue) and deep/muscular fasciae. The aim of the study was to assess the percentage of elastic fibres between superficial and deep fascia. MATERIALS AND METHODS Three full thickness specimens (proximal, middle and distal respectively) were taken from each of four regions of the thigh of three non-embalmed cadavers: the anterior (Ant), the lateral (Lat), the posterior (Post) and the medial (Med) aspect. Thus, a total of 12 specimens were collected from each analysed thigh and histological Weigert Van Gieson stains was performed. Three sections per specimen were considered for the morphometric analysis. RESULTS In all the specimens the superficial and deep fasciae were clearly recognizable. The difference in percentage of elastic fibres between superficial and deep fasciae in same region for all four was highly significant (p

The present study compares the structure and composition of fascia lata in healthy subjects and in patients with hip osteoarthritis (OA), to evaluate any differences in the amount of Collagen type I, Collagen type III, and Hyaluronan. Fascia lata samples from voluntary healthy subjects and patients with OA were harvested during surgery. Collagen type I (COL I), III (COL III) antibody, and biotinylated hyaluronan binding protein (HABP) immunohistochemistry stainings were used to evaluate fascial morphology and COL I, COL III, and Hyaluronan (HA) content in both groups. Ten samples from healthy subjects and 11 samples from OA patients were collected. COL I was significantly more abundant in the OA group (p = 0.0015), with a median percentage positivity of 75.2 (IQR 13.11)%, while representing only 67 (IQR: 8.71)% in control cases. COL III, with median values of 9.5 (IQR 3.63)% (OA group) and 17.10 (IQR 11)% (control cases), respectively, showed significant reduction in OA patients (p = 0.002). HA showed a median value of 10.01 (IQR 8.11)% in OA patients, denoting significant decrease (p &lt, 0.0001) with respect to the control group median 39.31 (IQR 5.62)%. The observed differences suggest a relationship between fascial pathology and hip OA. The observed increase in COL I in OA patients, along with the reduction of COL III and HA, could lead to fascial stiffening, which could alter fascial mechanics and be linked to the development and symptoms of OA.

Ultrasound (US) imaging is being increasingly used by Physical and Rehabilitation Medicine (PRM) specialists to measure the thickness of abdominal muscles. The current study set out to assess the inter-rater reliability of US measurements of the thickness of the abdominal muscles/fasciae. Three raters (1 = orthopedic specialist, expert on fasciae; 2 = PRM resident; 3 = PRM specialist) with different levels of US training examined the abdominal muscles and fasciae of a healthy volunteer under supine resting and dynamic conditions following a standard US protocol. The probe was positioned along the right lateral abdominal wall at the height of the 12th rib: (1) above the umbilicus at the linea alba, (2) to the side of and approximately 2 cm from the umbilicus, (3) along the mammillary line, and (4) along the anterior axillary line. Each rater measured 17 anatomical structures six times during two sessions. The relative error of the measurements (intra-rater variability) was slightly higher for the fasciae than for the muscles, and during the dynamic condition than the resting condition. Inter-rater reliability was good under both conditions for the fasciae (Intraclass Correlation Coefficient = ICC = 0.83) and excellent for the muscles (ICC = 0.99). Knowledge of the fascial anatomy of the abdominal wall is essential for accurate ultrasound examinations and for improving reliability. These findings confirm that US imaging is a reliable, non-invasive, cost-effective instrument for evaluating the abdominal muscles/fasciae. Clin. Anat. 32:948-960, 2019. © 2019 Wiley Periodicals, Inc.

Simple Summary Diabetes mellitus and its complications are increasingly prevalent worldwide with severe impacts on patients and health care systems. Diabetic foot ulcers have an important impact on disability, morbidity, and mortality. The mechanism of diabetic wound chronicity has not yet been understood in a complete way. Regarding the involved soft tissues, little space has been given to the fasciae, even if nowadays there is more and more evidence of their role in proprioception, muscular force transmission, skin vascularization and tropism, and wound healing. Thus, we aimed to deepen the fascial involvement in diabetic wounds. Based on this review, we suggest that a clear scientific perception of fascial role can improve treatment strategies and create new perspectives of treatment. Abstract Wound healing is an intricate, dynamic process, in which various elements such as hyperglycemia, neuropathy, blood supply, matrix turnover, wound contraction, and the microbiome all have a role in this “out of tune” diabetic complex symphony, particularly noticeable in the complications of diabetic foot. Recently it was demonstrated that the fasciae have a crucial role in proprioception, muscular force transmission, skin vascularization and tropism, and wound healing. Indeed, the fasciae are a dynamic multifaceted meshwork of connective tissue comprised of diverse cells settled down in the extracellular matrix and nervous fibers; each constituent plays a particular role in the fasciae adapting in various ways to the diverse stimuli. This review intends to deepen the discussion on the possible fascial role in diabetic wounds. In diabetes, the thickening of collagen, the fragmentation of elastic fibers, and the changes in glycosaminoglycans, in particular hyaluronan, leads to changes in the stiffness, gliding, and the distribution of force transmission in the fasciae, with cascading repercussions at the cellular and molecular levels, consequently feeding a vicious pathophysiological circle. A clear scientific perception of fascial role from microscopic and macroscopic points of view can facilitate the identification of appropriate treatment strategies for wounds in diabetes and create new perspectives of treatment.

It is recognized that different fasciae have different type of innervation, but actually nothing is known about the specific innervation of the two types of deep fascia, aponeurotic and epymisial fascia. In this work the aponeurotic thoracolumbar fascia and the epymisial gluteal fascia of seven adult C57-BL mice were analysed by Transmission Electron Microscopy and floating immunohistochemistry with the aim to study the organization of nerve fibers, the presence of nerve corpuscles and the amount of autonomic innervation. The antibodies used were Anti-S100, Anti-Tyrosine Hydroxylase and Anti-PGP, specific for the Schwann cells forming myelin, the sympathetic nerve fibers, and the peripheral nerve fibers, respectively. The results showed that the fascial tissue is pervaded by a rhomboid and dense network of nerves. The innervation was statistically significantly lower in the gluteal fascia (2.78 ± 0.6% of positive area, 140.3 ± 31.6/mm2 branching points, nerves with 3.2 ± 0.6 mm length and 4.9 ± 0.2 µm thickness) with respect to the thoracolumbar fascia (9.01 ± 0.98% of innervated area, 500.9 ± 43.1 branching points/mm2, length of 87.1 ± 1.0 mm, thickness of 5.8 ± 0.2 µm). Both fasciae revealed the same density of autonomic nerve fibers (0.08%). Lastly, corpuscles were not found in thoracolumbar fascia. Based on these results, it is suggested that the two fasciae have different roles in proprioception and pain perception: the free nerve endings inside thoracolumbar fascia may function as proprioceptors, regulating the tensions coming from associated muscles and having a role in nonspecific low back pain, whereas the epymisial fasciae works to coordinate the actions of the various motor units of the underlying muscle.

Background: Fascial layers may play an important role in locomotor mechanics. Recent researches have revealed an association between increases of fascia thickness and reduced joint flexibility in patients with chronic pain. The purpose of this study was to measure and compare, through the use of ultrasound imaging, the thickness of the deep/crural fascia in different points of the leg as well as the epimysial fascia thickness at level 2 of anterior compartment of leg, in male basketball players with history of recurrent ankle sprain and in healthy participants. Methods: A cross-sectional study has been performed using ultrasound imaging to measure deep/crural fascia thickness of anterior, lateral and posterior compartment of the leg at different levels with a new protocol in a sample of 30 subjects, 15 basketball players and 15 healthy participants. Results: Findings of fascial thickness revealed statistically significant differences (p &lt, 0.01) in epimysial fascia thickness and in deep/crural fascia thickness between levels/compartments of the same group and between two groups. Moreover, Post 3 deep/crural fascia thicknesses (p &lt, 0.001) were decreased showing statistically significant difference for the basketball players group respect the healthy participants group. Conclusions: These findings suggested that the posterior compartment was thicker than anterior compartment, probably due to a postural reason in both groups. Moreover, they showed an increase of thickness of the epimysial fascia in basketball players with previous ankle sprains. This variability underlines the importance to assess the fasciae and to make results comparable.

Stretching exercises are integral part of the rehabilitation and sport. Despite this, the mechanism behind its proposed effect remains ambiguous. It is assumed that flexibility increases, e.g., action on muscle and tendon, respectively, but this is not always present in the stretching protocol of the exercises used. Recently, the fasciae have increased popularity and seems that they can have a role to define the flexibility and the perception of the limitation of the maximal range of motion (ROM). Deep fascia is also considered a key element to transmit load in parallel bypassing the joints, transmitting around 30% of the force generated during a muscular contraction. So, it seems impossible dividing the action of the muscles from the fasciae, but they have to be considered as a “myofascial unit”. The purpose of this manuscript is to evaluate the mechanical behavior of muscles, tendons, and fasciae to better understand how they can interact during passive stretching. Stress-strain values of muscle, tendon and fascia demonstrate that during passive stretching, the fascia is the first tissue that limit the elongation, suggesting that fascial tissue is probably the major target of static stretching. A better understanding of myofascial force transmission, and the study of the biomechanical behavior of fasciae, with also the thixotropic effect, can help to design a correct plan of stretching.

The fascia can be defined as a dynamic highly complex connective tissue network composed of different types of cells embedded in the extracellular matrix and nervous fibers: each component plays a specific role in the fascial system changing and responding to stimuli in different ways. This review intends to discuss the various components of the fascia and their specific roles; this will be carried out in the effort to shed light on the mechanisms by which they affect the entire network and all body systems. A clear understanding of fascial anatomy from a microscopic viewpoint can further elucidate its physiological and pathological characteristics and facilitate the identification of appropriate treatment strategies.

Currently, myofascial pain has become one of the main problems in healthcare systems. Research into its causes and the structures related to it may help to improve its management. Until some years ago, all the studies were focused on muscle alterations, as trigger points, but recently, fasciae are starting to be considered a new, possible source of pain. This systematic review has been conducted for the purpose of analyze the current evidence of the muscular/deep fasciae innervation from a histological and/or immunohistochemical point of view. A literature search published between 2000 and 2021 was made in PubMed and Google Scholar. Search terms included a combination of fascia, innervation, immunohistochemical, and different immunohistochemical markers. Of the 23 total studies included in the review, five studies were performed in rats, four in mice, two in horses, ten in humans, and two in both humans and rats. There were a great variety of immunohistochemical markers used to detect the innervation of the fasciae; the most used were Protein Gene Marker 9.5 (used in twelve studies), Calcitonin Gene-Related Peptide (ten studies), S100 (ten studies), substance P (seven studies), and tyrosine hydroxylase (six studies). Various areas have been studied, with the thoracolumbar fascia being the most observed. Besides, the papers highlighted diversity in the density and type of innervation in the various fasciae, going from free nerve endings to Pacini and Ruffini corpuscles. Finally, it has been observed that the innervation is increased in the pathological fasciae. From this review, it is evident that fasciae are well innerved, their innervation have a particular distribution and precise localization and is composed especially by proprioceptors and nociceptors, the latter being more numerous in pathological situations. This could contribute to a better comprehension and management of pain.

Background and objectives: Possible disorders after delivery may interfere with the quality of life. The aim of this study was to ascertain whether abdominal muscles and fasciae differ in women depending on whether they experienced transverse cesarean section (CS) or vaginal delivery (VA) in comparison with healthy nulliparous (NU). Materials and methods: The thicknesses of abdominal muscles and fasciae were evaluated by ultrasound in 13 CS, 10 VA, and 13 NU women (we examined rectus abdominis (RA), external oblique (EO), internal oblique (IO), transversus abdominis (TrA), total abdominal muscles (TAM = EO + IO + TrA), inter-rectus distance (IRD), thickness of linea alba (TLA), rectus sheath (RS), which includes anterior fascia of RS and posterior fascia of RS (P-RS), loose connective tissue between sublayers of P-RS (LCT), abdominal perimuscular fasciae (APF), which includes anterior fascia of EO, fasciae between EO, IO, and TrA, and posterior fascia of TrA). Data on pain intensity, duration, and location were collected. Results: Compared with NU women, CS women had wider IRD (p = 0.004), thinner left RA (p = 0.020), thicker right RS (p = 0.035) and APF (left: p = 0.001, right: p = 0.001), and IO dissymmetry (p = 0.009). VA women had thinner RA (left: p = 0.008, right: p = 0.043) and left TAM (p = 0.024), mainly due to left IO (p = 0.027) and RA dissymmetry (p = 0.035). However, CS women had thicker LCT (left: p = 0.036, right: p &lt, 0.001), APF (left: p = 0.014, right: p = 0.007), and right IO (p = 0.028) than VA women. There were significant correlations between pain duration and the affected fasciae/muscles in CS women. Conclusions: CS women showed significant alterations in both abdominal fasciae and muscle thicknesses, whereas VA women showed alterations mainly in muscles. Thinner RA and/or dissymmetric IO, wider IRD, and thicker LCT and APF after CS may cause muscle deficits and alteration of fascial gliding, which may induce scar, abdominal, low back, and/or pelvic pain.

The demonstrated expression of endocannabinoid receptors in myofascial tissue suggested the role of fascia as a source and modulator of pain. Fibroblasts can modulate the production of the various components of the extracellular matrix, according to type of stimuli: physical, mechanical, hormonal, and pharmacological. In this work, fascial fibroblasts were isolated from small samples of human fascia lata of the thigh, collected from three volunteer patients (two men, one woman) during orthopedic surgery. This text demonstrates for the first time that the agonist of cannabinoid receptor 2, HU-308, can lead to in vitro production of hyaluronan-rich vesicles only 3&ndash, 4 h after treatment, being rapidly released into the extracellular environment. We demonstrated that these vesicles are rich in hyaluronan after Alcian blue and Toluidine blue stainings, immunocytochemistry, and transmission electron microscopy. In addition, incubation with the antagonist AM630 blocked vesicles production by cells, confirming that release of hyaluronan is a cannabinoid-mediated effect. These results may show how fascial cells respond to the endocannabinoid system by regulating and remodeling the formation of the extracellular matrix. This is a first step in our understanding of how therapeutic applications of cannabinoids to treat pain may also have a peripheral effect, altering the biosynthesis of the extracellular matrix in fasciae and, consequently, remodeling the tissue and its properties.

Although the number of Ultrasound (US) imaging studies investigating the fascial layers are becoming more numerous, the majority tend to use different reference points and terminology to describe their findings. The current work set out to compare macroscopic and microscopic data of specimens of the fascial layers of the thigh with US imaging findings. Specimens of the different fascial layers of various regions of the thigh were collected for macroscopic and histological analyses from three fresh cadavers and compared with in vivo US images of the thighs of 20 healthy volunteers. The specimens showed that the subcutaneous tissue of the thigh is made up of three layers: a superficial adipose layer, a membranous layer/superficial fascia, and a deep adipose layer. The deep fascia is composed of an aponeurotic fascia, which envelops all the thigh muscles and is laterally reinforced by the iliotibial tract and an epimysial fascia, which is specific for each muscle. The morphometric measurements of the thickness of the superficial fascia were different (anterior: 153.2 ± 39.3 µm; medial: 128.4 ± 24.7 µm; lateral: 154 ± 28.9 µm; and posterior: 148.8 ± 33.2 µm) as were those of the deep fascia (anterior: 556.8 ± 176.2 µm; medial: 820.4 ± 201 µm; lateral: 1112 ± 237.9 µm; and posterior: 730.4 ± 186.5 µm). The US scans showed a clear picture of the superficial adipose tissue, the superficial fascia, and the deep adipose tissue, as well as the deep fasciae. The epimysial and aponeurotic fasciae of only some topographic areas could be independently identified. The US imaging findings confirmed that the superficial and deep fascia have different thicknesses, and they showed that the US measurements were always larger with respect to those produced by histological analysis (p

Persistent symptoms, most commonly pain, may remain after otherwise successful hip replacement surgery. Innervation of fascia and soft tissues has become increasingly important in etiopathogenesis of pain, but the relative importance of the various anatomical structures in the hip region is still not known. Innervation of skin, superficial adipose tissue, superficial fascia, deep adipose tissue, deep fascia, muscles, capsule, capsule ligament, ligamentum teres, and tendon in the human hip from 11 patients and 2 cadavers were quantified by staining with anti-S100 antibody for myelin-forming Schwann cells, to obtain the percentage of antibody positivity, density and mean diameter of the nerve fibers. The skin was the most highly innervated (0.73% ± 0.37% of positive area in patients; 0.80% ± 0.28% in cadavers); the tendon was the least innervated (0.07% ± 0.01% in patients, 0.07% ± 0.007% in cadavers). The muscles (vasto-lateral and gluteus medius) were the second most innervated structure according the percentage (0.31% ± 0.13% in living humans, 0.30% ± 0.07% in cadavers), but with only a few nerves, with large diameters (mean diameter 36.4 ± 13.4 µm). Instead, the superficial fasciae showed 0.22% ± 0.06% and 0.26% ± 0.05% of positive areas in living humans and cadavers, respectively. Fasciae were invaded by networks of small nerve fibers, revealing a possible role in pain. The superficial fascia was the second most highly innervated tissue after the skin, with a density of 33.0 ± 2.5/cm2 , and a mean nerve sizes of 19.1 ± 7.2 µm. Lastly, the capsule turned out to be poorly innervated (0.09%), showing that its removal does not necessarily lead to painful consequences. Statement of clinical significance: Deeper knowledge about the innervation of the soft tissue in the human hip joint will enhance study and understanding of the best surgical procedures to follow during hip arthroplasty to reduce post-operative pain.

The abdominal muscles are important for the stability of the lumbar region through the thoracolumbar fascia (TLF). However, there is not full agreement regarding the posterior transversal continuity of the external abdominal oblique muscle (EO) with the TLF. To clarify this point, 10 cadavers and computed tomography (CT) images from 27 subjects were used to evaluate the transversal continuity of the TLF with the abdominal muscles. The width of the fascial continuity of the EO with the posterior layer of TLF along the posterior border of the EO was also measured (40.70 ±3.92 mm). The epimysial fascia of the EO was in direct continuity with the posterior layer of TLF in eight cadavers and 23 CT images, whereas in two cadavers and four CT images, the epimysial fascia of the EO first fused with the fascia covering the latissimus dorsi, and then, both fasciae were in continuity with the posterior layer of TLF. Therefore, the transversal fascial continuity of the EO could explain the transmission of tension from the EO to the posterior layer of TLF and its importance in maintaining the stability of the lumbar spine through a hydraulic effect. Regarding fascial continuity in the trunk, and taking the EO into consideration, the TLF is formed by the fascia of all the abdominal muscles as the rectus sheath. In this manner, myofascial continuity between the TLF and the abdominal muscles is achieved through the aponeurosis and fascia, which ensures synchronization between the erector spinae and the rectus abdominis. Clin. Anat. 31:1092-1098, 2018. © 2018 Wiley Periodicals, Inc.

The objectives of this work was to conduct a comprehensive state-of-the art review of the current literature to identify any gaps or discrepancies and summarize the main challenges for obtaining a homogeneous evaluation of muscular fascia in healthy individuals. An electronic document search using key words and MeSH terms was performed with various databases. Two independent investigators were tasked with the screening of articles and data extraction. A critical appraisal of what is known was then conducted. The literature search identified 65 articles related to healthy facia in the various databases consulted and 20 articles were kept for the review. The thickest portion of the fascia lata (the iliotibial tract) and the plantar fascia are the most often studied muscular fasciae whereas there is paucity of studies on fascia related to other muscles in the body. US imaging is suitable to complement physical examination and for evaluating treatment outcomes. However, the small number of studies and the heterogeneity of the methods did not allow us to establish normal reference values for muscular fascia thickness and to provide strong recommendations about measurement protocols.

Hyaluronan occurs between deep fascia and muscle, facilitating gliding between these two structures, and also within the loose connective tissue of the fascia, guaranteeing the smooth sliding of adjacent fibrous fascial layers. It also promotes the functions of the deep fascia. In this study a new class of cells in fasciae is identified, which we have termed fasciacytes, devoted to producing the hyaluronan-rich extracellular matrix. Synthesis of the hyaluronan-rich matrix by these new cells was demonstrated by Alcian Blue staining, anti-HABP (hyaluronic acid binding protein) immunohistochemistry, and transmission electron microscopy. Expression of HAS2 (hyaluronan synthase 2) mRNA by these cells was detected and quantified using real time RT-PCR. This new cell type has some features similar to fibroblasts: they are positive for the fibroblast marker vimentin and negative for CD68, a marker for the monocyte-macrophage lineage. However, they have morphological features distinct from classical fibroblasts and they express the marker for chondroid metaplasia, S-100A4. The authors suggest that these cells represent a new cell type devoted to the production of hyaluronan. Since hyaluronan is essential for fascial gliding, regulation of these cells could affect the functions of fasciae so they could be implicated in myofascial pain. Clin. Anat. 31:667-676, 2018. © 2018 Wiley Periodicals, Inc.

Increased knowledge of the rich innervation of the deep fascia and its anatomical organization indicates the need to reevaluate maps of the dermatome according to the new findings. The authors present a distinction between dermatome and fasciatome, basing their approach to the literature on nerve root stimulation and comparing dermatomeric and myomeric maps. The former represents the portion of tissue composed of skin, hypodermis, and superficial fascia supplied by all the cutaneous branches of an individual spinal nerve; the latter includes the portion of deep fascia supplied by the same nerve root and organized according to force lines to emphasize the main directions of movement. The dermatome is important for esteroception, whereas the fasciatome is important for proprioception. If they are altered, the dermatome shows clearly localized pain and the fasciatome irradiating pain according to the organization of the fascial anatomy. Clin. Anat. 32:896-902, 2019. © 2019 Wiley Periodicals, Inc.

Persistent scar pain associated with healed surgical incisions after a trauma is a common and potentially debilitating type of fascial pain. At present, there is no universally effective treatment for persistent surgical or post-trauma scar pain. Herein we describe the successful objective diagnosis of debilitating scar pain by Ultrasound (US) imaging. The sonopalpation of the fasciae and subcutaneous tissues seems to be relevant to diagnose the real cause of the pain and why not to monitor the treatment.

This study investigated the connections between the median nerve paraneural sheath and myofascial structures near it, from both macroscopic and microscopic points of view. Four samples of median nerve and surrounding tissues were excised from nine non‐embalmed upper limbs for microscopic analysis. Ultrasound images were analysed in 21 healthy subjects and 16 carpal tunnel syndrome patients to evaluate median nerve transversal displacement during finger motion at carpal tunnel and forearm levels. An anatomical continuity between epimysium and paraneural sheath and a reduction of paraneural fat tissue from proximal to distal was found in all samples. Median nerve displacements at both levels were significantly reduced in carpal tunnel syndrome subjects (P

A concept consolidated in recent years is that tumor growth depends to a great extent on the micro-environment surrounding the tumor, which has a fundamental role in tumor progression and in determining the effectiveness of therapies. Our analysis focuses on chondrosarcoma, the second primary malignant bone tumor, resistant to both chemotherapeutic and radiation therapy. We quantified hyaluronan, one of the main components of the extracellular matrix, with the aim of comparing its amount in the connective tissue surrounding the tumor with intra-tumoral tissue and healthy fascia of the same anatomic district, viewed as a health control. We demonstrate that hyaluronan increased significantly in the peritumoral stroma compared with the healthy fascia, which showed an average amount according to the physical characteristics of body districts by a mean value of 26.9 μg/g. In the peritumoral stroma, the mean hyaluronan content reached 132.6 μg/g (mean value of 63.2 μg/g). The p-value was less than 0.01, showing a highly significant statistical difference. Surprisingly, no significant differences were detected as a function of age, gender, or tumor grade. The levels of hyaluronan were comparable in peritumoral and tumor tissues, although there were differences depending on the state of necrosis. In addition, data on the expression of hyaluronic acid synthetase showed a decrease of about 50% in peritumoral and tumor tissues, indicating alterations in hyaluronan turnover and synthesis. This work demonstrates a variation in hyaluronan contents around the chondrosarcoma, likely correlated with the aggressiveness and resistance to chemotherapy of this tumors. Statement of Clinical Significance: Deeper knowledge about the composition of the peritumoral stroma, rich in extracellular matrix, will enhance better study and understanding of the metastatic potential of tumors and their prognostic indices. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:503-509, 2019.

Recently, alterations in fascial gliding‐like movement have been invoked as critical in the etiology of myofascial pain. Various methods have been attempted for the relief of this major and debilitating clinical problem. Paramount have been attempts to restore correct gliding between fascial layers and the movement over bone, joint, and muscular structures. One of the key elements that underlies such fascial movement is hyaluronan. However, until now, the precise content of hyaluronan within fasciae has been unknown. This study quantifies for the first time the hyaluronan content of human fascial samples obtained from a variety of anatomic sites. Here, we demonstrate that the average amount varies according to anatomic site, and according to the different kinds of sliding properties of the particular fascia. For example, the fascia lata has 35 μg of hyaluronan per gram of tissue, similar to that of the rectus sheath (29 μg g(−1)). However, the types of fascia adherent to muscle contain far less hyaluronan: 6 μg g(−1) in the fascia overlying the trapezius and deltoid muscles. In the fascia that surrounds joints, the hyaluronan increases to 90 μg g(−1), such as in the retinacula of the ankle, where greater degrees of movement occur. Surprisingly, no significant differences were detected at any site as a function of age or sex (P‐value > 0.05, t‐test) with the sole exception of the plantar fascia. This work can provide a better understanding of the role of hyaluronan in fascia. It will facilitate a better comprehension of the modulation of the hyaluronan‐rich layer that occurs in relation to the various conditions that affect fascia, and the diverse factors that underlie the attendant pathologies.

Hyaluronan occurs between deep fascia and muscle, facilitating gliding between these two structures, and also within the loose connective tissue of the fascia, guaranteeing the smooth sliding of adjacent fibrous fascial layers. It also promotes the functions of the deep fascia. In this study a new class of cells in fasciae is identified, which we have termed fasciacytes, devoted to producing the hyaluronan-rich extracellular matrix. Synthesis of the hyaluronan-rich matrix by these new cells was demonstrated by Alcian Blue staining, anti-HABP (hyaluronic acid binding protein) immunohistochemistry, and transmission electron microscopy. Expression of HAS2 (hyaluronan synthase 2) mRNA by these cells was detected and quantified using real time RT-PCR. This new cell type has some features similar to fibroblasts: they are positive for the fibroblast marker vimentin and negative for CD68, a marker for the monocyte-macrophage lineage. However, they have morphological features distinct from classical fibroblasts and they express the marker for chondroid metaplasia, S-100A4. The authors suggest that these cells represent a new cell type devoted to the production of hyaluronan. Since hyaluronan is essential for fascial gliding, regulation of these cells could affect the functions of fasciae so they could be implicated in myofascial pain. Clin. Anat. 31:667-676, 2018. © 2018 Wiley Periodicals, Inc.

Although it is now recognized that women suffer from myofascial pain to a greater extent than men, and that the muscular fasciae can respond to hormonal stimuli, thanks to the expression of sex hormone receptors, how the fasciae can modify their structure under hormonal stimulation is not clear. In this work, an immunocytochemical analysis of collagen-I, collagen-III and fibrillin were carried out on fibroblasts isolated from human fascia lata after in vitro treatment with various levels of sex hormones β-estradiol and/or relaxin-1, according to the phases of a woman’s period (follicular, periovulatory, luteal, post-menopausal phases and pregnancy). This study demonstrates for the first time that fascial cells can modulate the production of some components of the extracellular matrix according to hormone levels, when treated with β-estradiol: collagen-I falls from 6% of positivity in the follicular phase to 1.9 in the periovulatory phase. However, after the addition of relaxin-1 to the cell culture, the production of extracellular matrix decreased and remained at the same level (1.7% of collagen-I, at both follicular and periovulatory levels of hormones). These results confirm the antifibrotic function of relaxin-1, thanks to its ability to reduce matrix synthesis. They are also a first step in our understanding of how some hormonal dysfunctions in women can cause a dysregulation of extracellular matrix production in fasciae.

Cannabinoid receptors have been localized in the central and peripheral nervous system as well as on cells of the immune system, but recent studies on animal tissue gave evidence for the presence of cannabinoid receptors in different types of tissues. Their presence was supposed also in myofascial tissue, suggesting that the endocannabinoid system may help resolve myofascial trigger points and relieve symptoms of fibromyalgia. However, until now the expression of CB1 (cannabinoid receptor 1) and CB2 (cannabinoid receptor 2) in fasciae has not yet been established. Small samples of fascia were collected from volunteers patients during orthopedic surgery. For each sample were done a cell isolation, immunohistochemical investigation (CB1 and CB2 antibodies) and real time RT-PCR to detect the expression of CB1 and CB2. Both cannabinoid receptors are expressed in human fascia and in human fascial fibroblasts culture cells, although to a lesser extent than the control gene. We can assume that the expression of mRNA and protein of CB1 and CB2 receptors in fascial tissue are concentrated into the fibroblasts. This is the first demonstration that the fibroblasts of the muscular fasciae express CB1 and CB2. The presence of these receptors could help to provide a description of cannabinoid receptors distribution and to better explain the role of fasciae as pain generator and the efficacy of some fascial treatments. Indeed the endocannabinoid receptors of fascial fibroblasts can contribute to modulate the fascial fibrosis and inflammation.