Degenerative Musculoskeletal Disease Research Articles

Exploring the Impact of Catechins on Bone Metabolism: A Comprehensive Review of Current Research and Future Directions.

Background/Objectives: Degenerative musculoskeletal diseases represent a global health problem due to the progressive deterioration of affected individuals. As a bioactive compound, catechins have shown osteoprotective properties by stimulating osteoblastic cells and inhibiting bone resorption. Thus, this review aimed to address the mechanism of action of catechins on bone tissue. Methods: The search was applied to PubMed without limitations in date, language, or article type. Fifteen articles matched the topic and objective of this review. Results: EGCG (epigallocatechin gallate) and epicatechin demonstrated action on the osteogenic markers RANKL, TRAP, and NF-κβ and expression of BMPs and ALP, thus improving the bone microarchitecture. Studies on animals showed the action of EGCG in increasing calcium and osteoprotegerin levels, in addition to regulating the transcription factor NF-ATc1 associated with osteoclastogenesis. However, it did not show any effect on osteocalcin and RANK. Regarding human studies, EGCG reduced the risk of fracture in a dose-dependent manner. In periodontal tissue, EGCG reduced IL-6, TNF, and RANKL in vitro and in vivo. Human studies showed a reduction in periodontal pockets, gingival index, and clinical attachment level. The action of EGCG on membranes and hydrogels showed biocompatible and osteoinductive properties on the microenvironment of bone tissue by stimulating the expression of osteogenic growth factors and increasing osteocalcin and alkaline phosphate levels, thus promoting new bone formation. Conclusions: EGCG stimulates cytokines related to osteogenes, increasing bone mineral density, reducing osteoclastogenesis factors, and showing great potential as a therapeutic strategy for reducing the risk of bone fractures.

Applications of type I and II collagen in osteochondral tissue engineering: Respective features and future perspectives

At present, osteoarthritis stands as one of the most prevalent degenerative musculoskeletal diseases globally. The inherent lack of self-healing capacity in articular cartilage presents a considerable obstacle in treating osteoarthritis. Tissue engineering emerged as a promising strategy for the regeneration of osteochondral defects. Collagen, a primary component of bone and cartilage, stands out as a widely utilized natural material in osteochondral tissue engineering. Among various collagen types, Type I and type II collagen are notably prominent in this field. This review initially summarizes the advantageous and disadvantageous properties of type I/II collagen in osteochondral tissue engineering, proceeds to introduce their applications in this context, and concludes with a prospective outlook on the future development of type I/II collagen's applications.

Assessment of Surgical Outcomes in Patients with Degenerative Cervical Myelopathy Using the 25-Question Geriatric Locomotive Function Scale: A Longitudinal Observational Study.

Locomotive syndrome caused by degenerative musculoskeletal diseases is reported to improve with surgical treatment. However, it is unclear whether surgical treatment is effective for the locomotive syndrome developing in patients with degenerative cervical myelopathy (DCM). Thus, this study primarily aimed to longitudinally assess the change in locomotive syndrome stage before and after cervical spinal surgery for patients with DCM using the 25-question geriatric locomotive function scale (GLFS-25). A secondary objective was to identify factors associated with the postoperative improvement in the locomotive syndrome stage. We retrospectively reviewed clinical data of patients undergoing cervical spine surgery at our institution from April 2020 to May 2022 who had answered the Japanese Orthopaedic Association Cervical Myelopathy Assessment Questionnaire, visual analog scale, and GLFS-25 preoperatively and at 6 months and 1 year postoperatively. We collected demographic data, medical history, preoperative radiographic parameters, presence or absence of posterior longitudinal ligament ossification, and surgical data. We enrolled 115 patients (78 men and 37 women) in the present study. Preoperatively, using the GLFS-25, 73.9% of patients had stage 3, 10.4% had stage 2, 9.6% had stage 1, 6.1% had no locomotive syndrome. The stage distribution of locomotive syndrome improved significantly at 6-months and 1-year postoperatively. The multivariable Poisson regression analysis revealed that better preoperative lower extremity function (relative risk: 3.0; 95% confidence interval: 1.01-8.8) was significantly associated with postoperative improvement in the locomotive syndrome stage. This is the first study to longitudinally assess the locomotive syndrome stage in patients with DCM using GLFS-25. Our results indicated that patients with DCM experienced significant improvement in the locomotive syndrome stage following cervical spine surgery. Particularly, the preoperative lower extremity function was significant in postoperative improvement in the locomotive syndrome stage.

OA13 Alkaptonuria: a big mimic

Abstract Background/Aims Alkaptonuria is a rare metabolic disorder, often misdiagnosed as spondyloarthritis or degenerative musculoskeletal disease. The population most affected are young males in their 30s with characteristic arthritis involving the spine and large joints. The patient may notice their urine turning dark on standing and pigmentation over the skin and connective tissues (ochronosis); however, these subtle features may sometimes go unnoticed. Methods A 38-year-old-male with long standing back pain presented with right knee swelling. With a diagnosis of spondyloarthritis, he was previously treated with DMARDS but did not have any relief. There was a history of urine turning dark on standing. On examination, there was subtle hyperpigmentation over left ear concha and a spot on the sclera. An x-ray of the thoracic spine showed flattening and calcification of intervertebral disc spaces at multiple levels. Aspiration of synovial fluid showed suspended fragments of articular cartilage. His inflammatory markers were negative. We performed gas chromatography mass spectrometry which showed elevated excretion of homogentisic acid (HGA). A homozygous pathogenic variant in the homogentisate 1,2-dioxygenase gene associated with alkaptonuria was reported on whole genome sequencing. Results Ochronotic arthropathy is defined as progressive degenerative joint disease mainly affecting the spine and large joints. Most patients require at least one joint replacement by age 55. Small joints of hands and feet and sacroiliac joints are usually spared. Arthroscopy of the joint may reveal dark brown to black pigmented cartilage defects. The synovium may show fragments of pigmented cartilage suspended in the fluid (ground pepper sign). Plain spine radiographs may show flattening and calcifications of the intervertebral discs with a characteristic vacuum phenomenon (radiolucent gas collection). Periarticular structures like tendons and ligaments are also affected, leading to rupture in around 20-30% of patients. Alkaptonuria is also associated with decreased bone mineral density and subsequent risk for fragility fracture. Conclusion Alkaptonuria often mimics ankylosing spondylitis. A triad of ochronosis, dark urine and ochronotic arthropathy is the key to diagnosis. Definitive diagnosis is through biochemical or genetic testing. Nitisinone has proved to be effective but shows significant side effects. Management mainly involves physiotherapy and palliative care. Disclosure M. Shah: None. S. Upadhyaya: None.

Clinical results in patients affected by moderate-severe knee osteoarthritis and treated with micro-fragmented adipose tissue: the therapeutic effects on symptomatology.

Osteoarthrosis is a degenerative musculoskeletal disease that presents a major public health problem, due to the increasing average age of the active population, as well as the increasing percentage of obesity or overweight of the general population. New therapeutic approaches have been developed, such as regenerative medicine that uses mesenchymal stromal cells taken from adipose tissue. This study analyzed the clinical potential benefits of using autologous adipose tissue to treat patients with moderate-severe knee osteoarthritis.In 2021, a total of 50 knees, affected by moderate-severe knee osteoarthritis, were treated with an intra-articular injection of micro-fragmented subcutaneous adipose tissue. Patients were submitted to the KOOS questionnaire before the operation and one year after the operation and VAS pain score at time 0, 3, 6, 12 months.Of the 50 patients treated, 2 patients were excluded from the study. Of the remaining 48 patients, improvements have been achieved in all subclasses of KOOS. In particular, VAS score proves that improvements are more considerable starting from the 3rd month after surgery.The results obtained in this study show the safety and potential benefit of the use of autologous micro-fragmented adipose on people who are affected by moderate-severe knee osteoarthritis.

Gaussian Aquila optimizer based dual convolutional neural networks for identification and grading of osteoarthritis using knee joint images

Degenerative musculoskeletal disease known as Osteoarthritis (OA) causes serious pain and abnormalities for humans and on detecting at an early stage, timely treatment shall be initiated to the patients at the earliest to overcome this pain. In this research study, X-ray images are captured from the humans and the proposed Gaussian Aquila Optimizer based Dual Convolutional Neural Networks is employed for detecting and classifying the osteoarthritis patients. The new Gaussian Aquila Optimizer (GAO) is devised to include Gaussian mutation at the exploitation stage of Aquila optimizer, which results in attaining the best global optimal value. Novel Dual Convolutional Neural Network (DCNN) is devised to balance the convolutional layers in each convolutional model and the weight and bias parameters of the new DCNN model are optimized using the developed GAO. The novelty of the proposed work lies in evolving a new optimizer, Gaussian Aquila Optimizer for parameter optimization of the devised DCNN model and the new DCNN model is structured to minimize the computational burden incurred in spite of it possessing dual layers but with minimal number of layers. The knee dataset comprises of total 2283 knee images, out of which 1267 are normal knee images and 1016 are the osteoarthritis images with an image of 512 × 512-pixel width and height respectively. The proposed novel GAO-DCNN system attains the classification results of 98.25% of sensitivity, 98.93% of specificity and 98.77% of classification accuracy for abnormal knee case–knee joint images. Experimental simulation results carried out confirms the superiority of the developed hybrid GAO-DCNN over the existing deep learning neural models form previous literature studies.

Genetics may affect the risk of undergoing surgery for rhizarthrosis.

Osteoarthritis is a prevalent and severe disease. Involvement of the trapeziometacarpal joint is common and can lead to both pain and disability. Genetics are known to affect the risk of osteoarthritis, but it remains unclear how genetics affect disease trajectories. In this study, we investigated whether the genetic associations of trapeziometacarpal osteoarthritis (rhizarthrosis) vary with the need for surgical treatment. The study was conducted as a case-control genome-wide association study using individuals from the Copenhagen Hospital Biobank pain and degenerative musculoskeletal disease study and the Danish Blood Donor Study (N = 208,342). We identified patients diagnosed with rhizarthrosis and grouped them by treatment status, resulting in two case groups: surgical (N = 1083) and nonsurgical (N = 1888). The case groups were tested against osteoarthritis-free controls in two genome-wide association studies. We then compared variants suggestive of association (p < 10-6) in either of these analyses directly between the treatment groups (surgical vs. nonsurgical rhizarthrosis). We identified 10 variants suggestive of association with either surgical (seven variants) or nonsurgical (three variants) rhizarthrosis. None of the variants reached nominal significance in the opposite treatment group (p ≥ 0.14), and all 10 variants were significantly different between the treatment groups at a false discovery rate of 5%. These results suggest possible differences in the genetic associations of rhizarthrosis depending on surgical treatment. Clinical significance: Uncovering genetic differences between clinically distinct patient groups can reveal biological determinants of disease trajectories.

Harnessing exosomes for advanced osteoarthritis therapy.

Exosomes are nanosized, lipid membrane vesicles secreted by cells, facilitating intercellular communication by transferring cargo from parent to recipient cells. This capability enables biological crosstalk across multiple tissues and cells. Extensive research has been conducted on their role in the pathogenesis of degenerative musculoskeletal diseases such as osteoarthritis (OA), a chronic and painful joint disease that particularly affects cartilage. Currently, no effective treatment exists for OA. Given that exosomes naturally modulate synovial joint inflammation and facilitate cartilage matrix synthesis, they are promising candidates as next generation nanocarriers for OA therapy. Recent advancements have focused on engineering exosomes through endogenous and exogenous approaches to enhance their joint retention, cartilage and chondrocyte targeting properties, and therapeutic content enrichment, further increasing their potential for OA drug delivery. Notably, charge-reversed exosomes that utilize electrostatic binding interactions with cartilage anionic aggrecan glycosaminoglycans have demonstrated the ability to penetrate the full thickness of early-stage arthritic cartilage tissue following intra-articular administration, maximizing their therapeutic potential. These exosomes offer a non-viral, naturally derived, cell-free carrier for OA drug and gene delivery applications. Efforts to standardize exosome harvest, engineering, and property characterization methods, along with scaling up production, will facilitate more efficient and rapid clinical translation. This article reviews the current state-of-the-art, explores opportunities for exosomes as OA therapeutics, and identifies potential challenges in their clinical translation.

Prodigy Long-Established Solution in Degenerative Musculoskeletal Disease as Vishwachi with Special Reference to Cervical Spondylosis - A Novel Case Report

A rectifier that is a unique merger of the two utterly non-identical therapeutic procedures, namely Viddhakarma (piercing) and Agnikarma(thermal cauterization), collectively termed "Viddhagnikarma." It is a modification of the concept by the types of Agni karma procedure developed byAcharya Sushrut that states the use of different instruments for Agni karma at different sites. As muscles, tendons, and ligaments are deep structures, theheat produced must reach them via a medium that bypasses the skin to prevent skin burn, so viddhagnikarma was brought into play. Vishwachi can becorrelated to cervical spondylosis as they both have the same signs and symptoms. Vishwachi is most commonly found in the geriatric age group withsymptoms of morning stiffness at the cervical region, difficulty in neck movements, radiating pain, tingling sensation in the upper limb, and difficulty inneck movements. The study aims to relieve pain and regression in other symptoms by restoring normal neck and arm movements without adverseeffects. NSAID and many more have been more aggressively used and have to be replaced by some alternative therapy that is safe in the geriatric agegroup that is cheap comparatively.This case study introduces a therapeutic regimen called viddhagnikarma for pain management in an 81-year-old ladydiagnosed with Vishwachi (cervical spondylosis) that presented with no relief from topical analgesics and muscle relaxants. The patient has great reliefwithin two sittings, i.e., after 7 days, with no adverse effects.

Chair Fitness Program for Improved Strength and Physical Function for Older Adults: A Pilot Comparative Effectiveness Study

Within the US, people are experiencing longer life expectancy, yet these extended lifespans have not necessarily translated into years living in good health. Musculoskeletal degenerative diseases are particularly prevalent amongst older adults. Research shows that regular resistance exercise carries preventive health benefits to combat these conditions. This study evaluated the impact of an innovative hand-held device (OYO) on the physical function of older adults compared to a traditional chair fitness program (CF) and no exercise control (CG). Participants (n = 48) were 60 years old and older, retirement community residents with no current history of chronic conditions, who possessed the ability to follow guided exercise. Participants elected to the OYO, CF or CG groups. The exercise program was 45 minutes, twice a week for 9 weeks. The CF group used standard gym equipment while the OYO group utilized a hand-held device capable of multi-planar movements and varying resistance. Various pre-post measures of physical function were recorded. Preliminary data suggests that there was a significant positive difference between the study group for biceps strength test F(2, 39) = 3.49 p = 0.04, h&lt;sup&gt;2&lt;/sup&gt; = 0.15), 30-second chair stand (F(2, 37) = 3.60, p = 0.04, h&lt;sup&gt;2&lt;/sup&gt; = 0.16) and a 2-min step test (F(2, 39) = 3.27 p = 0.05, h&lt;sup&gt;2&lt;/sup&gt; = 0.14). A Tukey-HSD test showed a positive trending, however, not significant effect for 30-second chair stand and latissimus strength test (p = 0.08 and 0.06, respectively) between the OYO and CF groups. The two groups had equivocal post-intervention results on all other measures. In conclusion, our results suggest this hand-held device is as or more efficacious as a traditional resistance program that utilizes several pieces of equipment. Widespread adoption of this device could reduce program costs and improve access to quality fitness opportunities for older adults.

Novel insights of EZH2-mediated epigenetic modifications in degenerative musculoskeletal diseases.

Degenerative musculoskeletal diseases (Osteoporosis, Osteoarthritis, Degenerative Spinal Disease and Sarcopenia) are pathological conditions that affect the function and pain of tissues such as bone, cartilage, and muscles, and are closely associated with ageing and long-term degeneration. Enhancer of zeste homolog 2 (EZH2), an important epigenetic regulator, regulates gene expression mainly through the PRC2-dependent trimethylation of histone H3 at lysine 27 (H3K27me3). Increasing evidence suggests that EZH2 is involved in several biological processes closely related to degenerative musculoskeletal diseases, such as osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells, osteoclast activation, chondrocyte functional status, and satellite cell proliferation and differentiation, mainly through epigenetic regulation (H3K27me3). Therefore, the synthesis and elucidation of the role of EZH2 in degenerative musculoskeletal diseases have attracted increasing attention. In addition, although EZH2 inhibitors have been approved for clinical use, whether they can be repurposed for the treatment of degenerative musculoskeletal diseases needs to be considered. Here, we reviewed the role of EZH2 in the development of degenerative musculoskeletal diseases and brought forward prospects of its pharmacological inhibitors in the improvement of the treatment of the diseases.

Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m6 modification

Although cigarette smoking (CS) and low back pain (LBP) are common worldwide, their correlations and the mechanisms of action remain unclear. We have shown that excessive activation of mast cells (MCs) and their proteases play key roles in CS-associated diseases, like asthma, chronic obstructive pulmonary disease (COPD), blood coagulation, and lung cancer. Previous studies have also shown that MCs and their proteases induce degenerative musculoskeletal disease. By using a custom-designed smoke-exposure mouse system, we demonstrated that CS results in intervertebral disc (IVD) degeneration and release of MC-restricted tetramer tryptases (TTs) in the IVDs. TTs were found to regulate the expression of methyltransferase 14 (METTL14) at the epigenetic level by inducing N6-methyladenosine (m6A) deposition in the 3' untranslated region (UTR) of the transcript that encodes dishevelled-axin (DIX) domain-containing 1 (DIXDC1). That reaction increases the mRNA stability and expression of Dixdc1. DIXDC1 functionally interacts with disrupted in schizophrenia 1 (DISC1) to accelerate the degeneration and senescence of nucleus pulposus (NP) cells by activating a canonical Wnt pathway. Our study demonstrates the association between CS, MC-derived TTs, and LBP. These findings raise the possibility that METTL14-medicated DIXDC1 m6A modification could serve as a potential therapeutic target to block the development of degeneration of the NP in LBP patients.

Cell-Based Therapies for Degenerative Musculoskeletal Diseases.

Degenerative musculoskeletal diseases (DMDs), including osteoporosis, osteoarthritis, degenerative disc disease, and sarcopenia, present major challenges in the aging population. Patients with DMDs present with pain, functional decline, and reduced exercise tolerance, which result in long-term or permanent deficits in their ability to perform daily activities. Current strategies for dealing with this cluster of diseases focus on relieving pain, but they have a limited capacity to repair function or regenerate tissue. Cell-based therapies have attracted considerable attention in recent years owing to their unique mechanisms of action and remarkable effects on regeneration. In this review, current experimental attempts to use cell-based therapies for DMDs are highlighted, and the modes of action of different cell types and their derivatives, such as exosomes, are generalized. In addition, the latest findings from state-of-the-art clinical trials are reviewed, approaches to improve the efficiency of cell-based therapies are summarized, and unresolved questions and potential future research directions for the translation of cell-based therapies are identified.

Prevalence of Symptomatic and Asymptomatic Rotator Cuff Tears in General Population Attending Health Care Camps at Tertiary Care Hospital

Background: With the aging society, musculoskeletal degenerative diseases are becoming a burden on Society, and rotator cuff disease is one of these degenerative diseases. The purpose of this study was to examine the incidence of Rotator cuff tear is the most common shoulder disease in patients with shoulder problems, at tertiary care hospital. Material and methods: A total of 700 patients examined. Ultrasonography on bilateral shoulders was performed in all the participants. Results: 165 subjects out of 700 participants (23.5%) had full-thickness rotator cuff tears. The prevalence of rotator cuff tear in each decade was 0% in the 20s to 40s, 14.7% in the 50s, 21.5% in the 60s, 31.2% in the 70s, and 32.6% in the 80s. Symptomatic rotator cuff tears accounted for 32.2% of all tears and asymptomatic tears for 67.8%. The prevalence of asymptomatic rotator cuff tears was one-half of all tears in the 50s, whereas it accounted for two-thirds of those over the age of 60. The prevalence of tear was significantly greater in male than in female in the 50s and 60s, but not in the 70s and 80s. Conclusion: The prevalence of rotator cuff tear in the general population was 21%, which increased with age. Asymptomatic tear was twice as common as symptomatic tear.

The Role of Lubricin, Irisin and Exercise in the Prevention and Treatment of Osteoarthritis

Osteoarthritis is a chronic degenerative musculoskeletal disease that worsens with age and is defined by pathological alterations in joint components. All clinical treatment recommendations for osteoarthritis promote exercise, although precise molecular pathways are unclear. The purpose of this study was to critically analyze the research on lubricin and irisin and how they relate to healthy and diseased joint tissue. Our research focused specifically on exercise strategies and offered new perspectives for future potential osteoarthritis treatment plans. Although lubricin and irisin have only recently been discovered, there is evidence that they have an impact on cartilage homeostasis. A crucial component of cartilage lubrication and integrity, lubricin is a surface-active mucinous glycoprotein released by the synovial joint. Its expression increases with joint movement. In healthy joints, lubricin molecules cover the cartilage surface to lubricate the boundary of the joint and inhibit protein and cell attachment. Patients with joint trauma, inflammatory arthritis, or genetically mediated lubricin deficiency, who do not produce enough lubricin to protect the articular cartilage, develop arthropathy. Irisin, sometimes known as the "sports hormone", is a myokine secreted primarily by skeletal muscle. It is a physiologically active protein that can enter the circulation as an endocrine factor, and its synthesis and secretion are primarily triggered by exercise-induced muscle contraction. We searched PubMed, Web of Science, Google Scholar, and Scopus using the appropriate keywords to identify the most recent research. The studies considered advance our knowledge of the role that exercise plays in the fight against osteoarthritis, serve as a valuable resource, and support the advancement of osteoarthritis prevention and therapy.

Platelet-Rich Plasma Gel Matrix (PRP-GM): Description of a New Technique.

Several musculoskeletal conditions are triggered by inflammatory processes that occur along with imbalances between anabolic and catabolic events. Platelet-rich plasma (PRP) is an autologous product derived from peripheral blood with inherent immunomodulatory and anabolic properties. The clinical efficacy of PRP has been evaluated in several musculoskeletal conditions, including osteoarthritis, tendinopathy, and osteonecrosis. When used in combination with hyaluronic acid (HA), a common treatment alternative, the regenerative properties of PRP are significantly enhanced and may provide additional benefits in terms of clinical outcomes. Recently, a new PRP-derived product has been reported in the literature and is being referred to as "plasma gel". Plasma gels are obtained by polymerizing plasmatic proteins, which form solid thermal aggregates cross-linked with fibrin networks. Plasma gels are considered to be a rich source of growth factors and provide chemotactic, migratory, and proliferative properties. Additionally, clot formation and the associated fibrinolytic reactions play an additional role in tissue repair. There are only a few scientific articles focusing on plasma gels. Historically, they have been utilized in the fields of aesthetics and dentistry. Given that the combination of three products (PRP, HA, and plasma gel) could enhance tissue repair and wound healing, in this technical note, we propose a novel regenerative approach, named "PRP-HA cellular gel matrix" (PRP-GM), in which leukocyte-rich PRP (LR-PRP) is mixed with a plasma gel (obtained by heating the plasma up) and HA in one syringe using a three-way stopcock. The final product contains a fibrin-albumin network entangled with HA's polymers, in which the cells and biomolecules derived from PRP are attached and released gradually as fibrinolytic reactions and hyaluronic acid degradation occur. The presence of leukocytes, especially monocytes and macrophages, promotes tissue regeneration, as type 2 macrophages (M2) possess an anti-inflammatory feature. In addition, HA promotes the viscosuplementation of the joint and induces an anti-inflammatory response, resulting in pain relief. This unique combination of biological molecules may contribute to the optimization of regenerative protocols suitable for the treatment of degenerative musculoskeletal diseases.

Intraovarian Injection of Reconstituted Lyophilized Growth-Promoting Factor Extracted from Horse Blood Platelets (L-GFequina) Increases Oocytes Recovery and In Vitro Embryo Production in Holstein Cows.

Simple SummaryLyophilized horse-platelet-derived growth factor (L-GFequina) is a brand-new, improved platelet-rich protein growth factor. It has been successfully used to treat a number of inflammatory and degenerative musculoskeletal diseases in several disciplines of regenerative medicine. Our study aimed to evaluate the possibility of using an intraovarian injection of L-GFequina in the assisted reproduction of Holstein cows. L-GFequina employs allogenic, pathogen-free platelets from horses that have been successfully used in other species to prevent changes in technical platelet specifications caused by the centrifugation process and time, as well as the integrity and quality of autologous platelets. The number of ovum pick-up (OPU) sessions per cycle, the growth of medium- and large-sized follicles, the number of COCs produced per cow per session, and the formation of blastocysts during OPU-IVEP in eCG stimulated Holstein cows were all boosted in this study by an intraovarian injection of L-GFequina.The purpose of this study was to determine the impact of intraovarian injections of a reconstituted lyophilized growth-promoting factor extracted from horse blood platelets (L-GFequina) on the number of ovarian follicles, the recovery of cumulus–oocyte complexes (COCs), and embryo development to the blastocyst stage in Holstein cows. Thus, 12 Holstein cows were assigned to three protocols. According to the number of punctured follicles in protocol 1, ovum pick-up (OPU) was conducted on days 6 and 14 of the cycle (day 0 = estrus). In protocol 2, every large follicle (more than 7 mm) was removed, and 1 mL of L-GFequina was intraovarian injected (day 0). Two days later, equine chorionic gonadotropin (eCG) was administered, and OPU sessions were conducted on days 6, 10, and 14. The same ovarian stimulation procedure as that in protocol 2 was performed in protocol 3, except that equine L-GFequina was not supplied. OPU was carried out on days 6 and 10 of the cycle. The results indicate that the intraovarian injection of L-GFequina significantly (p < 0.05) increased the number of OPU sessions per cycle, the recovery of cumulus–oocyte complexes (COCs), and the production of blastocysts. In conclusion, an intraovarian injection of L-GFequina can improves OPU-IVEP results in Holstein cows.

Exercise-induced modulation of myokine irisin in bone and cartilage tissue-Positive effects on osteoarthritis: A narrative review.

Osteoarthritis is a chronic degenerative musculoskeletal disease characterized by pathological changes in joint structures along with the incidence of which increases with age. Exercise is recommended for all clinical treatment guidelines of osteoarthritis, but the exact molecular mechanisms are still unknown. Irisin is a newly discovered myokine released mainly by skeletal muscle in recent years—a biologically active protein capable of being released into the bloodstream as an endocrine factor, the synthesis and secretion of which is specifically induced by exercise-induced muscle contraction. Although the discovery of irisin is relatively recent, its role in affecting bone density and cartilage homeostasis has been reported. Here, we review the production and structural characteristics of irisin and discuss the effects of the different types of exercise involved in the current study on irisin and the role of irisin in anti-aging. In addition, the role of irisin in the regulation of bone mineral density, bone metabolism, and its role in chondrocyte homeostasis and metabolism is reviewed. A series of studies on irisin have provided new insights into the mechanisms of exercise training in improving bone density, resisting cartilage degeneration, and maintaining the overall environmental homeostasis of the joint. These studies further contribute to the understanding of the role of exercise in the fight against osteoarthritis and will provide an important reference and aid in the development of the field of osteoarthritis prevention and treatment.

Role of Caspase Family in Intervertebral Disc Degeneration and Its Therapeutic Prospects.

Intervertebral disc degeneration (IVDD) is a common musculoskeletal degenerative disease worldwide, of which the main clinical manifestation is low back pain (LBP); approximately, 80% of people suffer from it in their lifetime. Currently, the pathogenesis of IVDD is unclear, and modern treatments can only alleviate its symptoms but cannot inhibit or reverse its progression. However, in recent years, targeted therapy has led to new therapeutic strategies. Cysteine-containing aspartate proteolytic enzymes (caspases) are a family of proteases present in the cytoplasm. They are evolutionarily conserved and are involved in cell growth, differentiation, and apoptotic death of eukaryotic cells. In recent years, it has been confirmed to be involved in the pathogenesis of various diseases, mainly by regulating cell apoptosis and inflammatory response. With continuous research on the pathogenesis and pathological process of IVDD, an increasing number of studies have shown that caspases are closely related to the IVDD process, especially in the intervertebral disc (IVD) cell apoptosis and inflammatory response. Therefore, herein we study the role of caspases in IVDD with respect to the structure of caspases and the related signaling pathways involved. This would help explore the strategy of regulating the activity of the caspases involved and develop caspase inhibitors to prevent and treat IVDD. The aim of this review was to identify the caspases involved in IVDD which could be potential targets for the treatment of IVDD.

Hyperbaric Oxygen and Regenerative Medicine: Non-Traditional Uses to Help Reduce Inflammation, Stimulate Cell Regeneration and Improve Healing

Hyperbaric oxygen therapy (HBOT) is US FDA approved for a short list of 14 severe, life-threatening conditions. These FDA approved conditions range from osteomyelitis, osteonecrosis and gangrene to non-healing wounds, diabetic neuropathy, crush injuries, radiation burns and more. When applied in acute and severe conditions, this therapy is noninvasive, safe, and effective in promoting patient recovery, improved healing times, and increased tissue regeneration. Alternatively, chronic inflammatory illnesses affect a larger population, cost our medical system billions of dollars every year, impair our quality of life, and reduce our ability to contribute to society. Some of these conditions include autoimmunity, neurodegenerative and musculoskeletal degenerative diseases, cardiovascular disease, cancer and many others. Common denominators for many of these illnesses include chronic inflammation, metabolic and mitochondrial dysfunction and immune dysregulation. The majority of studies for HBOT point to about 10 very specific mechanisms of action when used for the more conventionally treated conditions. There is mounting evidence that the mechanisms of action for these “on label” acute and severe cases are similar or even identical to those required for treating other chronic illnesses to improve their outcomes and recovery times. Hyperbaric oxygen can be delivered a number of ways, from mild pressure to high pressure and from 21% oxygen through 100% oxygen. Current research also shows that intermittent and relative hyperoxia-hypoxia is a strong stimulator of many cell signaling and epigenetic signaling cascades used for the promotion of and adaptation to improved cellular healing and regenerative responses. The research on these concepts is currently in its infancy but recent studies have shown that HBOT, through its influences on hypoxia-inducible factor 1α, reactive oxygen species signaling and sirtuin stimulation can help to promote hormonal balance, nervous system balance, improve mitochondrial performance, reduce inflammation and stimulate cell and tissue repair and regeneration for many different health concerns. Another study published in 2019 also showed us that using hyperbaric oxygen can also stimulate telomere growth and reduce cellular senescence, putting HBOT within the category of optimal modalities to be considered for a well-rounded antiaging and regenerative medicine approach to improved health and quality of life.