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Cureus Jun 2023Osteoarthritis (OA) is a common chronic degenerative disease. The prevalence tends to increase with age and is influenced by underlying risk factors such as gender,... (Review)
Review
Osteoarthritis (OA) is a common chronic degenerative disease. The prevalence tends to increase with age and is influenced by underlying risk factors such as gender, obesity, joint injuries (work/sports activities), and geographic region. OA has a distinctive picture, namely, damage to the joint cartilage and the formation of new bone at the edges of the bones, also called osteophytes, due to biochemical, metabolic, physiological, and pathological changes in the joint cartilage and subchondral bone. Symptoms that can be caused include joint pain, inhibition of joint movement, crepitus, deformity, asymmetrical swelling of the joints, signs of inflammation, and changes in gait. Currently, there are various methods of managing OA in terms of reducing pain, including regeneration and non-regeneration therapy. Non-regeneration treatments include physiotherapy (exercise, biomechanical intervention, electrotherapy, diathermy), pharmacology, intra-articular injections (corticosteroids, hyaluronic acid, geniculate nerve blocks), extra-articular injections, and radiofrequency. In comparison, regeneration management includes laser and intra-articular injection (prolotherapy and PRP).
PubMed: 37503484
DOI: 10.7759/cureus.40966 -
Annals of the Rheumatic Diseases Nov 2023Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in...
OBJECTIVES
Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of deficiency on the development of post-traumatic and age-associated OA in mice.
METHODS
Male cartilage-specific -deficient mice and intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery. Age-associated OA was assessed in mice aged 12 and 18 months of age. OA severity was analysed by micro-CT, histomorphometry and scoring of articular cartilage structure, toluidine blue staining and osteophyte formation. SIRT6-regulated pathways were analysed in human chondrocytes by RNA-sequencing, qRT-PCR and immunoblotting.
RESULTS
deficient mice displayed enhanced DMM-induced OA severity and accelerated age-associated OA when compared with controls, characterised by increased cartilage damage, osteophyte formation and subchondral bone sclerosis. In chondrocytes, RNA-sequencing revealed that depletion significantly repressed cartilage extracellular matrix (eg, ) and anabolic growth factor (eg, insulin-like growth factor-1 ()) gene expression. Gain-of-function and loss-of-function studies in chondrocytes demonstrated that SIRT6 depletion attenuated, whereas adenoviral overexpression or MDL-800-induced activation promoted IGF-1 signalling by increasing Akt phosphorylation.
CONCLUSIONS
SIRT6 deficiency increases post-traumatic and age-associated OA severity in vivo. SIRT6 profoundly regulated the pro-anabolic and pro-survival IGF-1/Akt signalling pathway and suggests that preserving the SIRT6/IGF-1/Akt axis may be necessary to protect cartilage from injury-associated or age-associated OA. Targeted therapies aimed at increasing SIRT6 function could represent a novel strategy to slow or stop OA.
Topics: Male; Animals; Mice; Humans; Aged; Insulin-Like Growth Factor I; Osteophyte; Proto-Oncogene Proteins c-akt; Osteoarthritis; Chondrocytes; Cartilage, Articular; RNA; Sirtuins; Disease Models, Animal
PubMed: 37550003
DOI: 10.1136/ard-2023-224385 -
Frontiers in Cell and Developmental... 2023Osteoarthritis (OA) is one of the leading causes of pain and disability in the elderly. Synovitis, cartilage destruction and osteophyte formation histologically manifest... (Review)
Review
Osteoarthritis (OA) is one of the leading causes of pain and disability in the elderly. Synovitis, cartilage destruction and osteophyte formation histologically manifest OA. Unfortunately, there is currently no effective therapy to delay its progression and the underlying mechanisms of OA require further exploration. Macrophage is a main cellular component of joint synovium. It is highly plastic and can be stimulated to polarize to different phenotypes, namely, the pro-inflammatory phenotype (M1) and the anti-inflammatory/tissue-repairing phenotype (M2). Ample evidence has demonstrated the vital roles of macrophages in the progression of OA. Imbalanced M1/M2 ratio is significantly related to OA severity indicating macrophage polarization might be a promising therapeutic target for OA. In this review, we summarized the involvements of polarized macrophages in synovitis, cartilage degradation, osteophyte formation and OA-related chronic pain. Promising therapies targeting macrophage polarization including the intra-articular cell/derivates-based therapy and the alternative non-invasive intervention such as photobiomodulation therapy were reviewed as well.
PubMed: 37954210
DOI: 10.3389/fcell.2023.1269724 -
Advanced Science (Weinheim,... Sep 2023The microenvironment and stem cell fate guidance of post-traumatic articular cartilage regeneration is primarily the focus of cartilage tissue engineering. In articular... (Review)
Review
The microenvironment and stem cell fate guidance of post-traumatic articular cartilage regeneration is primarily the focus of cartilage tissue engineering. In articular cartilage, stem cells are characterized by overlapping lineages and uneven effectiveness. Within the first 12 weeks after trauma, the articular inflammatory microenvironment (AIME) plays a decisive role in determining the fate of stem cells and cartilage. The development of fibrocartilage and osteophyte hyperplasia is an adverse outcome of chronic inflammation, which results from an imbalance in the AIME during the cartilage tissue repair process. In this review, the sources for the different types of stem cells and their fate are summarized. The main pathophysiological events that occur within the AIME as well as their protagonists are also discussed. Additionally, regulatory strategies that may guide the fate of stem cells within the AIME are proposed. Finally, strategies that provide insight into AIME pathophysiology are discussed and the design of new materials that match the post-traumatic progress of AIME pathophysiology in a spatial and temporal manner is guided. Thus, by regulating an appropriately modified inflammatory microenvironment, efficient stem cell-mediated tissue repair may be achieved.
Topics: Humans; Regeneration; Tissue Engineering; Stem Cells; Cartilage, Articular; Wound Healing; Arthritis
PubMed: 37518822
DOI: 10.1002/advs.202207715 -
Frontiers in Cell and Developmental... 2023Knee osteoarthritis (KOA) is manifested by low-grade joint inflammation, irreversible cartilage degeneration, subchondral bone remodeling and osteophyte formation. It is... (Review)
Review
Knee osteoarthritis (KOA) is manifested by low-grade joint inflammation, irreversible cartilage degeneration, subchondral bone remodeling and osteophyte formation. It is one of the most prevalent degenerative diseases in the elderly. KOA usually results in chronic joint pain, physical impairment even disability bringing a huge socioeconomic burden. Unfortunately, there is so far no effective interventions to delay the progression and development of KOA. There is a pressing need for explorations and developments of new effective interventions. Photobiomodulation therapy (PBMT), also known as low-level light therapy (LLLT), has attracted widespread attention in treating KOA because it is drug-free, non-invasive, safe and useful with rarely reported side effects. It provides the biological stimulatory effects primarily by enhancing the activity of mitochondrial cytochrome c oxidase. This stimulation, in turn, fosters cell proliferation and tissue regeneration. In addition to this, the paper provides a concise overview of the light parameters and the effectiveness of PBMT when applied in the treatment of KOA patients in clinical settings. It also delves into the experimental evidence supporting the modulatory effects of PBMT and its potential underlying mechanisms in addressing synovitis, cartilage degeneration, and pain resolution.
PubMed: 38033853
DOI: 10.3389/fcell.2023.1286025 -
Cureus Dec 2023Degenerative cervical myelopathy (DCM) is a spinal condition of growing importance due to its increasing prevalence within the ageing population. DCM involves the... (Review)
Review
Degenerative cervical myelopathy (DCM) is a spinal condition of growing importance due to its increasing prevalence within the ageing population. DCM involves the degeneration of the cervical spine due to various processes such as disc ageing, osteophyte formation, ligament hypertrophy or ossification, as well as coexisting congenital anomalies. This article provides an overview of the literature on DCM and considers areas of focus for future research. A patient with DCM can present with a variety of symptoms ranging from mild hand paraesthesia and loss of dexterity to a more severe presentation of gait disturbance and loss of bowel/bladder control. Hoffman's sign and the inverted brachioradialis reflex are also important signs of this disease. The gold standard imaging modality is MRI which can identify signs of degeneration of the cervical spine. Other modalities include dynamic MRI, myelography, and diffusion tensor imaging. One important scoring system to aid with the diagnosis and categorisation of the severity of DCM is the modified Japanese Orthopaedic Association score. This considers motor, sensory, and bowel/bladder dysfunction, and categorises patients into mild, moderate, or severe DCM. DCM is primarily treated with surgery as this can halt disease progression and may even allow for neurological recovery. The surgical approach will depend on the location of degeneration, the number of cervical levels involved and the pathophysiological process. Surgical approach options include anterior cervical discectomy and fusion, corpectomy, or posterior approach (laminectomy ± fusion). Conservative management is also considered for some patients with mild or non-progressive DCM or for patients where surgery is not an option. Conservative treatment may include physical therapy, traction, or neck immobilisation. Future recommendations include research into the prevalence rate of DCM and if there is a difference between populations. Further research on the benefit of conservative management for patients with mild or non-progressive DCM would be recommended.
PubMed: 38213348
DOI: 10.7759/cureus.50387 -
Foot & Ankle Orthopaedics Jul 2023Arthritis of the first metatarsophalangeal (MTP) joint, hallux rigid, is a common and disabling source of foot pain in the adult population. Hallux rigidus is... (Review)
Review
Arthritis of the first metatarsophalangeal (MTP) joint, hallux rigid, is a common and disabling source of foot pain in the adult population. Hallux rigidus is characterized by diseased cartilage and large, periarticular osteophytes that result in a stiff, painful joint. Activity modification, sensible shoes, orthotics, anti-inflammatory medications and occasional intra-articular steroid injections can be attempted to alleviate the discomfort associated with hallux rigidus. A number of surgical options exist for the treatment of recalcitrant hallux rigidus. Cheilectomy is a useful treatment for dorsal impingement pain seen in mild hallux rigidus. A new polyvinyl alcohol hemi-arthroplasty implant has shown promising early and midterm results in the treatment of advanced hallux rigidus; however, arthrodesis of the first MTP joint remains the gold standard treatment for advanced hallux rigidus because of unpredictable outcomes after early-generation joint replacement implants.
PubMed: 37506124
DOI: 10.1177/24730114231188123