Extracellular Vesicles and Exosomes in the Control of the Musculoskeletal Health.

PURPOSE OF REVIEW: The present review will highlight recent reports supporting the relevance of extracellular vesicles to the musculoskeletal system in health and disease. RECENT FINDINGS: Preserving the health of the musculoskeletal system is important to maintain a good quality of life, and the bone-muscle crosstalk is crucial in this regard. This latter is largely mediated by extracellular vesicles released by the different cell populations residing in muscle and bone, which deliver cargoes, microRNAs, and proteins being the most relevant ones, to target cells. Extracellular vesicles could be exploited as therapeutic tools, in view of their resistance to destruction in the biological fluid and of the possibility to be functionalized according to the need. Extracellular vesicles are recognized as crucial players in the bone-muscle cross-talk. Additional studies however are required to refine their use as biomarkers of early alterations of the musculoskeletal system, and as potential therapeutic tools.

The role of PIEZO ion channels in the musculoskeletal system.

PIEZO1 and PIEZO2 are mechanosensitive cation channels that are highly expressed in numerous tissues throughout the body and exhibit diverse, cell-specific functions in multiple organ systems. Within the musculoskeletal system, PIEZO1 functions to maintain muscle and bone mass, sense tendon stretch, and regulate senescence and apoptosis in response to mechanical stimuli within cartilage and the intervertebral disc. PIEZO2 is essential for transducing pain and touch sensations as well as proprioception in the nervous system, which can affect musculoskeletal health. PIEZO1 and PIEZO2 have been shown to act both independently as well as synergistically in different cell types. Conditions that alter PIEZO channel mechanosensitivity, such as inflammation or genetic mutations, can have drastic effects on these functions. For this reason, therapeutic approaches for PIEZO-related disease focus on altering PIEZO1 and/or PIEZO2 activity in a controlled manner, either through inhibition with small molecules, or through dietary control and supplementation to maintain a healthy cell membrane composition. Although many opportunities to better understand PIEZO1 and PIEZO2 remain, the studies summarized in this review highlight how crucial PIEZO channels are to musculoskeletal health and point to promising possible avenues for their modulation as a therapeutic target.

Musculoskeletal Deficits and Cognitive Impairment: Epidemiological Evidence and Biological Mechanisms.

PURPOSE OF REVIEW: Cognitive impairment is associated with obesity, sarcopenia, and osteoporosis. However, no critical appraisal of the literature on the relationship between musculoskeletal deficits and cognitive impairment, focusing on the epidemiological evidence and biological mechanisms, has been published to date. Herein, we critically evaluate the literature published over the past 3 years, emphasizing interesting and important new findings, and provide an outline of future directions that will improve our understanding of the connections between the brain and the musculoskeletal system. RECENT FINDINGS: Recent literature suggests that musculoskeletal deficits and cognitive impairment share pathophysiological pathways and risk factors. Cytokines and hormones affect both the brain and the musculoskeletal system; yet, lack of unified definitions and standards makes it difficult to compare studies. Interventions designed to improve musculoskeletal health are plausible means of preventing or slowing cognitive impairment. We highlight several musculoskeletal health interventions that show potential in this regard.

Sp7 Action in the Skeleton: Its Mode of Action, Functions, and Relevance to Skeletal Diseases.

Osteoblast differentiation is a tightly regulated process in which key transcription factors (TFs) and their target genes constitute gene regulatory networks (GRNs) under the control of osteogenic signaling pathways. Among these TFs, Sp7 works as an osteoblast determinant critical for osteoblast differentiation. Following the identification of Sp7 and a large number of its functional studies, recent genome-scale analyses have made a major contribution to the identification of a "non-canonical" mode of Sp7 action as well as "canonical" ones. The analyses have not only confirmed known Sp7 targets but have also uncovered its additional targets and upstream factors. In addition, biochemical analyses have demonstrated that Sp7 actions are regulated by chemical modifications and protein-protein interaction with other transcriptional regulators. Sp7 is also involved in chondrocyte differentiation and osteocyte biology as well as postnatal bone metabolism. The critical role of SP7 in the skeleton is supported by its relevance to human skeletal diseases. This review aims to overview the Sp7 actions in skeletal development and maintenance, particularly focusing on recent advances in our understanding of how Sp7 functions in the skeleton under physiological and pathological conditions.

Muscle Research: A Tour d'Horizon.

The Special Issue on the "Muscular Structure, Physiology and Metabolism" was proposed in order to maintain the referenced scientific community abreast with recent research advancements regarding the morphology, functionality, and metabolism of muscle tissue, including a total of eighteen published papers, of which twelve were original research manuscripts and six were review papers [...].

COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives.

COVID-19 is a trending topic worldwide due to its immense impact on society. Recent trends have shifted from acute effects towards the long-term morbidity of COVID-19. In this review, we hypothesize that SARS-CoV-2 contributes to age-related perturbations in endothelial and adipose tissue, which are known to characterize the early aging process. This would explain the long-lasting symptoms of SARS-CoV-2 as the result of an accelerated aging process. Connective tissues such as adipose tissue and musculoskeletal tissue are the primary sites of aging. Therefore, current literature was analyzed focusing on the musculoskeletal symptoms in COVID-19 patients. Hypovitaminosis D, increased fragility, and calcium deficiency point towards bone aging, while joint and muscle pain are typical for joint and muscle aging, respectively. These characteristics could be classified as early osteoarthritis-like phenotype. Exploration of the impact of SARS-CoV-2 and osteoarthritis on endothelial and adipose tissue, as well as neuronal function, showed similar perturbations. At a molecular level, this could be attributed to the angiotensin-converting enzyme 2 expression, renin-angiotensin system dysfunction, and inflammation. Finally, the influence of the nicotinic cholinergic system is being evaluated as a new treatment strategy. This is combined with the current knowledge of musculoskeletal aging to pave the road towards the treatment of long-term COVID-19.

The emerging role of miR-128 in musculoskeletal diseases.

MicroRNA-128 (miR-128) is associated with cell proliferation, differentiation, migration, apoptosis, and survival. Genetic analysis studies have demonstrated that miR-128 participates in bone metabolism, which involves bone marrow-derived mesenchymal stem cells, osteoblasts, osteoclasts, and adipocytes. miR-128 also participates in regeneration of skeletal muscles by targeting myoblast-associated proteins. The deregulation of miR-128 could lead to a series of musculoskeletal diseases. In this review, we discuss recent findings of miR-128 in relation to bone metabolism and muscle regeneration to determine its potential therapeutic effects in musculoskeletal diseases, and to propose directions for future research in this significant field.

The molecular mechanisms of probiotic strains in improving ageing bone and muscle of d-galactose-induced ageing rats.

AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system. METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P < 0·05). Strain L. fermentum DR9 demonstrated improved expression of SOD in bone and muscle compared to the aged rats (P < 0·05). In the evaluation of myogenesis-related genes, L. paracasei OFS 0291 and L. fermentum DR9 increased the mRNA expression of IGF-1; L. helveticus OFS 1515 and L. fermentum DR9 reduced the expression of MyoD, in contrast to the aged controls (P < 0·05). Protective effects of L. fermentum DR9 on ageing muscle were believed to be contributed by increased AMPK-α2 expression. Among the osteoclastogenesis genes studied, TNF-α expression was highly elevated in tibia of aged rats, while all three probiotics strains ameliorated the expression. Lactobacillus fermentum DR9 also reduced the expression of IL-6 and TRAP in tibia when compared to the aged rats (P < 0·05). All probiotics treatment resulted in declined proinflammatory cytokines IL-1ß in muscle and bone. CONCLUSIONS: Lactobacillus fermentum DR9 appeared to be the strongest strain in modulation of musculoskeletal health during ageing. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrated the protective effects of the bacteria on muscle and bone through antioxidative and anti-inflammatory actions. Therefore, L. fermentum DR9 may serve as a promising targeted anti-ageing therapy.

Proinflammatory Diet Increases Circulating Inflammatory Biomarkers and Falls Risk in Community-Dwelling Older Men.

BACKGROUND: The relations between diet, chronic inflammation, and musculoskeletal health are unclear, especially among older men. OBJECTIVE: This study aimed to determine associations of the Dietary Inflammatory Index (DII) with inflammatory biomarkers, musculoskeletal health, and falls risk in community-dwelling older men. METHODS: The cross-sectional analysis included 794 community-dwelling men, mean age 81.1 ± 4.5 y, who participated in the 5-y follow-up of the Concord Health and Aging in Men Project. Of these, 616 were seen again 3 y later for the longitudinal analysis. Energy-adjusted DII (E-DII) was calculated from a validated diet history questionnaire. Bone mineral density (BMD) was measured using DXA. Twenty-four inflammatory biomarkers were analyzed. Incident falls over 3 y were determined through telephone interviews every 4 mo. Multiple regression, linear mixed effects models, negative binomial regression, and mediation analysis were utilized in this study. RESULTS: A higher E-DII score (indicating a more proinflammatory diet) was associated with higher concentrations of IL-6 (ß: 0.028 pg/mL; 95% CI: 0.003, 0.053), IL-7 (ß: 0.020 pg/mL; 95% CI: 0.002, 0.037), and TNF-α (ß: 0.027 pg/mL; 95% CI: 0.003, 0.051). A higher E-DII score was also associated with lower appendicular lean mass adjusted for BMI (ALMBMI) (ß: -0.006 kg/m2; 95% CI: -0.010, -0.001). For every unit increase in E-DII (range: -4.91 to +3.66 units), incident falls rates increased by 13% (incidence rate ratio: 1.13; 95% CI: 1.05, 1.21) over 3 y. Mediation analysis showed that the association between E-DII and 3-y incident falls was influenced by the concentrations of IL-7 by 24%. There was no association between E-DII and BMD. CONCLUSIONS: Consumption of a proinflammatory diet was associated with increased concentrations of IL-6, IL-7, and TNF-α; increased falls risk; and lower ALMBMI in community-dwelling older men. The association between incident falls and E-DII was partly mediated by concentrations of IL-7.

The Latest Evidence from Vitamin D Intervention Trials for Skeletal and Non-skeletal Outcomes.

Vitamin D has long been considered a central part of the treatment paradigm for osteoporosis. Initial studies in high-risk populations with widespread vitamin D deficiency found a reduction of both vertebral and non-vertebral fractures. Subsequent studies in the general population have yielded mixed but mostly disappointing results both for skeletal and especially non-skeletal outcomes. Recent sequential trial meta-analyses suggest that future studies are likely to be futile given the overall disappointing result. However, mega-trials are still in progress, and additional results have been released. This narrative review aims to evaluate new literature to determine if there has been any substantial change in the message. In conclusion, there is no longer a strong case for initiating vitamin D alone trials in the general adult population, irrespective of age and gender, for significant health outcomes such as fractures, cardiovascular disease and cancer. New studies should focus on risk groups and take directions from the Heaney criteria for evaluation of threshold nutrients. Indeed, real benefits may still be reaped by directing vitamin D supplementation to persons with proven or likely vitamin D deficiency. Further, the role of dietary calcium as a critical co-nutrient remains controversial and could contribute to the discrepancy between studies in terms of cancer outcomes and possibly falls and fractures.

The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging.

Although aging is considered a normal process, there are cellular and molecular changes that occur with aging that may be detrimental to health. Osteoporosis is one of the most common age-related degenerative diseases, and its progression correlates with aging and decreased capacity for stem cell differentiation and proliferation in both men and women. Tryptophan metabolism through the kynurenine pathway appears to be a key factor in promoting bone-aging phenotypes, promoting bone breakdown and interfering with stem cell function and osteogenesis; however, little data is available on the impact of tryptophan metabolites downstream of kynurenine. Here we review available data on the impact of these tryptophan breakdown products on the body in general and, when available, the existing evidence of their impact on bone. A number of tryptophan metabolites (e.g., 3-hydroxykynurenine (3HKYN), kynurenic acid (KYNA) and anthranilic acid (AA)) have a detrimental effect on bone, decreasing bone mineral density (BMD) and increasing fracture risk. Other metabolites (e.g., 3-hydroxyAA, xanthurenic acid (XA), picolinic acid (PIA), quinolinic acid (QA), and NAD+) promote an increase in bone mineral density and are associated with lower fracture risk. Furthermore, the effects of other tryptophan breakdown products (e.g., serotonin) are complex, with either anabolic or catabolic actions on bone depending on their source. The mechanisms involved in the cellular actions of these tryptophan metabolites on bone are not yet fully known and will require further research as they are potential therapeutic targets. The current review is meant as a brief overview of existing English language literature on tryptophan and its metabolites and their effects on stem cells and musculoskeletal systems. The search terms used for a Medline database search were: kynurenine, mesenchymal stem cells, bone loss, tryptophan metabolism, aging, and oxidative stress.

Tissue-Specific Decellularization Methods: Rationale and Strategies to Achieve Regenerative Compounds.

The extracellular matrix (ECM) is a complex network with multiple functions, including specific functions during tissue regeneration. Precisely, the properties of the ECM have been thoroughly used in tissue engineering and regenerative medicine research, aiming to restore the function of damaged or dysfunctional tissues. Tissue decellularization is gaining momentum as a technique to obtain potentially implantable decellularized extracellular matrix (dECM) with well-preserved key components. Interestingly, the tissue-specific dECM is becoming a feasible option to carry out regenerative medicine research, with multiple advantages compared to other approaches. This review provides an overview of the most common methods used to obtain the dECM and summarizes the strategies adopted to decellularize specific tissues, aiming to provide a helpful guide for future research development.

Genetics of Bone and Muscle Interactions in Humans.

PURPOSE OF REVIEW: To summarize the evidence from recent studies on the shared genetics between bone and muscle in humans. RECENT FINDINGS: Genome-wide association studies (GWAS) have successfully identified a multitude of loci influencing the variability of different bone or muscle parameters, with multiple loci overlapping between the traits. In addition, joint analyses of multiple correlated musculoskeletal traits (i.e., multivariate GWAS) have underscored several genes with possible pleiotropic effects on both bone and muscle including MEF2C and SREBF1. Notably, several of the proposed pleiotropic genes have been validated using human cells or animal models. It is clear that the study of pleiotropy may provide novel insights into disease pathophysiology potentially leading to the identification of new treatment strategies that simultaneously prevent or treat both osteoporosis and sarcopenia. However, the role of muscle factors (myokines) that stimulate bone metabolism, as well as osteokines that affect muscles, is in its earliest stage of understanding.

Lumbar muscle and vertebral bodies segmentation of chemical shift encoding-based water-fat MRI: the reference database MyoSegmenTUM spine.

BACKGROUND: Magnetic resonance imaging (MRI) is the modality of choice for diagnosing and monitoring muscular tissue pathologies and bone marrow alterations in the context of lower back pain, neuromuscular diseases and osteoporosis. Chemical shift encoding-based water-fat MRI allows for reliable determination of proton density fat fraction (PDFF) of the muscle and bone marrow. Prior to quantitative data extraction, segmentation of the examined structures is needed. Performed manually, the segmentation process is time consuming and therefore limiting the clinical applicability. Thus, the development of automated segmentation algorithms is an ongoing research focus. CONSTRUCTION AND CONTENT: This database provides ground truth data which may help to develop and test automatic lumbar muscle and vertebra segmentation algorithms. Lumbar muscle groups and vertebral bodies (L1 to L5) were manually segmented in chemical shift encoding-based water-fat MRI and made publically available in the database MyoSegmenTUM. The database consists of water, fat and PDFF images with corresponding segmentation masks for lumbar muscle groups (right/left erector spinae and psoas muscles, respectively) and lumbar vertebral bodies 1-5 of 54 healthy Caucasian subjects. The database is freely accessible online at https://osf.io/3j54b/?view_only=f5089274d4a449cda2fef1d2df0ecc56 . CONCLUSION: A development and testing of segmentation algorithms based on this database may allow the use of quantitative MRI in clinical routine.

Vitamin D history part III: the "modern times"-new questions for orthopaedic practice: deficiency, cell therapy, osteomalacia, fractures, supplementation, infections.

PURPOSE: The nutritional basis for rickets was described between 1880 and 1915, at the same period of discovery of other "vital substances" or vitamins. In contrast, rickets could also be prevented or cured by sunshine. But as the capacity to produce vitamin D depends on exposure to ultraviolet B rays (UVB) from sunlight or artificial sources, vitamin D became one of the most frequently used "drugs" in the twentieth century to compensate for insufficient exposure to UVB of humans. Furthermore, as the understanding of vitamin D metabolism grew during the twentieth century, other concerns than rickets occurred for the orthopaedic surgeon: In recent history, deficiency is explored as being an associated factor of different bone pathologies as fracture or prosthetic infection. The aim of this review is to analyze these new data on vitamin D. MATERIALS AND METHODS: During the twentieth century, there were many concerns for the orthopaedic surgeon: sources and synthesis of vitamin D, regulation of the calcium deposition process for both children and adults, when vitamin D deficiency is observed, and what the best method of vitamin D supplementation is. As target genes regulated by vitamin D are not limited to those involved in mineral homeostasis, orthopedists recently discovered that vitamin D might prevent periprosthetic infection. RESULTS: The primary source (80%) of vitamin D is dermal synthesis related to the sun. Dietary sources (20%) of vitamin D are fat fishe, beef, liver, and eggs. Vitamin D is produced industrially to be used in fortified foods and supplements. Maintenance of skeletal calcium balance is mediated through vitamin D receptors. Progenitor cells, chondrocytes, osteoblasts, and osteoclasts contain these receptors which explains the role of vitamin D in cell therapy, in the prevention of rickets and osteomalacia. Despite fortified foods, the prevalence of deficiency remains endemic in north latitudes. However, the definition of vitamin D insufficiency or deficiency remains controversial. Vitamin D has been evaluated in patients undergoing fractures and elective orthopaedic procedures Although supplementation may not be able to prevent or cure all the orthopaedic pathologies, oral supplementation is able to improve the vitamin D levels of deficient patients. These vitamin D level improvements might be associated with better functional and clinical outcomes after some surgical procedures and improvement of immunity to decrease the risk of infection in arthroplasties. CONCLUSION: Vitamin D deficiency is frequent and concerns millions of people in the world. It is therefore normal to find hypovitaminosis in various orthopaedic populations including trauma and arthroplasties. However, we do not know exactly if this phenomenon only reflects the general prevalence of vitamin D deficiency or has an influence on the outcome of some pathologies on specific populations at risk. After the success of treatment of rickets, it is disappointing that we are still wondering in the twenty-first century whether supplementation of a substance synthetized millions of years ago by plankton and necessary for growth of all the animals may improve (or not) clinical and functional outcomes of a simple fracture in humans.

Transforming Growth Factor Beta 3-Loaded Decellularized Equine Tendon Matrix for Orthopedic Tissue Engineering.

Transforming growth factor beta 3 (TGFß3) promotes tenogenic differentiation and may enhance tendon regeneration in vivo. This study aimed to apply TGFß3 absorbed in decellularized equine superficial digital flexor tendon scaffolds, and to investigate the bioactivity of scaffold-associated TGFß3 in an in vitro model. TGFß3 could effectively be loaded onto tendon scaffolds so that at least 88% of the applied TGFß3 were not detected in the rinsing fluid of the TGFß3-loaded scaffolds. Equine adipose tissue-derived multipotent mesenchymal stromal cells (MSC) were then seeded on scaffolds loaded with 300 ng TGFß3 to assess its bioactivity. Both scaffold-associated TGFß3 and TGFß3 dissolved in the cell culture medium, the latter serving as control group, promoted elongation of cell shapes and scaffold contraction (p < 0.05). Furthermore, scaffold-associated and dissolved TGFß3 affected MSC musculoskeletal gene expression in a similar manner, with an upregulation of tenascin c and downregulation of other matrix molecules, most markedly decorin (p < 0.05). These results demonstrate that the bioactivity of scaffold-associated TGFß3 is preserved, thus TGFß3 application via absorption in decellularized tendon scaffolds is a feasible approach.

Bone marrow aspirate clot: A technical complication or a smart approach for musculoskeletal tissue regeneration?

One of the methods employed to improve healing of damaged tissues is the use of cellular based therapies. A number of regenerative medicine based strategies, from in vitro expanded mesenchymal stem cells (MSCs) to "one-step" procedures using bone marrow (BM) in toto (BM aspirate; BMA) or BM concentrate (BMC), have been developed. Recently, orthopedic researchers focused their attention on the clinical therapeutic potential of BMC and BMA for musculoskeletal regeneration. BMA is reported as an excellent source of cells and growth factors. However, the quality of BM harvest and aspirate is extremely technique-dependent and, due to the presence of megakaryocytes and platelets, BMA is prone to clot. BMA clot formation is usually considered a complication hampering the procedures on both BMC preparation and MSC expansion. Therefore, different protocols have been developed to avoid and/or degrade clots. However, from a biological point of view there is a strong rationale for the use of BMA clot for tissue engineering strategies. This descriptive systematic literature review summarizes preclinical and clinical studies dealing the use of BMA clot for orthopedic procedures and provided some evidence supporting its use as a cell based therapy for cartilage and bone regeneration. Despite these results, there are still few preclinical and clinical studies that carefully evaluate the safety and efficacy of BMA clot in orthopedic procedures. Thus, implementing biological knowledge and both preclinical and clinical studies could help researchers and clinicians to understand if BMA clots can really be considered a possible therapeutic tool.

The use of cell conditioned medium for musculoskeletal tissue regeneration.

Tissue regenerative medicine combines the use of cells, scaffolds, and molecules to repair damaged tissues. Different cell types are employed for musculoskeletal diseases, both differentiated and mesenchymal stromal cells (MSCs). In recent years, the hypothesis that cell-based therapy is guided principally by cell-secreted factors has become increasingly popular. The aim of the present literature review was to evaluate preclinical and clinical studies that used conditioned medium (CM), rich in cell-factors, for musculoskeletal regeneration. Thirty-one were in vitro, 12 in vivo studies, 1 was a clinical study, and 2 regarded extracellular vesicles. Both differentiated cells and MSCs produce CM that induces reduction in inflammation and increases synthetic activity. MSC recruitment and differentiation, endothelial cell recruitment and angiogenesis have also been observed. In vivo studies were performed with CM in bone and periodontal defects, arthritis and muscle dystrophy pathologies. The only clinical study was performed with CM from MSCs in patients needing alveolar bone regeneration, showing bone formation and no systemic or local complications. Platelet derived growth factor receptor ß, C3a, vascular endothelial growth factor, monocyte chemoattractant protein-1 and -3, interleukin 3 and 6, insulin-like growth factor-I were identified as responsible of cell migration, proliferation, osteogenic differentiation, and angiogenesis. The use of CM could represent a new regenerative treatment in several musculoskeletal pathologies because it overcomes problems associated with the use of cells and avoids the use of exogenous GFs or gene delivery systems. However, some issues remain to be clarified.

Lapine periodontal ligament stem cells for musculoskeletal research in preclinical animal trials.

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) have been shown to be a reliable source of mesenchymal stem cells (MSCs). On the other hand, rabbits have been commonly used in preclinical trials for musculoskeletal research. However, there is a lack of sufficient data on using rabbit periodontal ligament stem cells (rPDLSCs) for regenerative dentistry. This study, for the first time, comprehensively compared rPDLSCs against hPDLSCs in terms of clonogenicity, growth potential, multi-differential capacity and surface antigens. METHODS: Periodontal ligament (PDL) was obtained from the rabbit and human teeth. rPDL and hPDL cells were isolated from PDL using enzymatic digestion method. After culturing for 2 weeks, the cells were first analyzed microscopically. STRO-1+CD146+ PDLSCs were then sorted from PDL cells by fluorescence-activated cell sorting (FACS) followed by examination of CD34, CD45, CD90, vimentin and desmin markers. The cells were also evaluated by immunohistocytochemical and multi-differentiation potential tests. The clonogenicity and growth of PDL cells were analyzed by Independent T test and 2-way repeated measures ANOVA respectively. RESULTS: rPDL cells were broader and less elongated as compared to hPDL cells. STRO-1+CD146+ hPDLSCs were isolated from hPDL cells but not from the rPDL cells. Therefore, heterogeneous population of rabbit and human PDL cells were subsequently used for latter comparative studies. FACS analysis and immunohistocytochemistry revealed that rPDL cells were partially positive for STRO-1 as compared to hPDL cells. Furthermore, both rPDL cells and hPDL cells were positive for CD146, CD90, vimentin, and desmin, while negative for CD34 and CD45. No difference in clonogenicity between rPDL and hPDL cells was found (p > 0.05). The proliferative potential of rPDL cells displayed significantly slower growth as compared to hPDL cells (p < 0.05). Osteogenic, adipogenic, and chondrogenic differentiation potential was comparatively less in rPDL cells than that of hPDL cells, but the neurogenic differential potential was similar. CONCLUSION: Although rPDL cells manifested variable differences in expression of stem cell markers and multi-differential potential as compared to hPDL cells, they demonstrated the attributes of stemness. Further studies are also required to validate if the regenerative potential of rPDL cells is similar to rPDLSCs.

The role of long non-coding RNA H19 in musculoskeletal system: A new player in an old game.

The long non-coding RNAs (lncRNAs) have gained much attention due to its essential roles in molecular regulation. As one of the classic lncRNAs, H19 is strongly expressed during embryogenesis and plays a crucial biological function during development. Mesenchymal stem cells (MSCs) are an ideal cell source for tissue engineering in musculoskeletal system as they own the multi-differentiation ability towards osteogenesis, adipogenesis, tenogenesis or chondrogenesis. In recent years, many studies have been found in the field of H19 mediated cellular differentiation of MSCs. Here, we summarized the current understanding of H19 during multi-differentiation of MSCs and its application in tissue regeneration of musculoskeletal system. Particularly, its molecular regulation and biological function during the multi-differentiation were also discussed.