EIJMRMS ISSN: 2750-8587
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GENETIC MECHANISMS OF OSTEOARTHRITIS OF THE FEMORAL HIP JOINT
Shodikulova Gulandom Zikriyayevna
Professor, Samarkand State Medical University, Samarkand, Uzbekistan
Gulomov Jahongir Ibrokhimovich
Assistant, Samarkand State Medical University, Samarkand, Uzbekistan
Pulatov Ulugbek Sunatovich
PhD, docent, Samarkand State Medical University, Samarkand, Uzbekistan
Khasanov Oybek Gafurovich
Assistant, Samarkand State Medical University, Samarkand, Uzbekistan
AB O U T ART I CL E
Key words:
Osteoarthritis (OA), genetic
mechanisms, COVID-19, SARS-CoV-2 virus,
femoral hip joint, genes encoding collagen (e.g.,
COL2A1), GDF5, Medications targeting molecular
targets, Cartilage metabolism genes, matrix
metalloproteinases (MMPs) and their inhibitors
(TIMPs).
Received:
02.08.2024
Accepted
: 07.08.2024
Published
: 12.08.2024
Abstract:
Osteoarthritis of the hip is a prevalent
degenerative joint disease characterized by
various genetic and environmental influences.
This review emphasizes the contributions of key
genetic mechanisms, particularly the COL2A1 and
GDF5 genes, to cartilage damage and the
pathogenesis of osteoarthritis. Genetic mutations,
polymorphisms, and variations in these genes are
linked to heightened risks and more severe
clinical presentations of osteoarthritis, especially
in patients following COVID-19. Furthermore,
additional genes involved in inflammatory
responses and cartilage metabolism also play a
crucial role in disease development. The insights
gained from genetic research may lead to
innovative approaches to early diagnosis,
personalized treatment plans, and improved
management strategies for osteoarthritis. Future
studies utilizing larger patient cohorts and
advanced genetic analysis methods are essential
to confirm these findings and enhance
understanding of osteoarthritis, ultimately
improving
preventive
and
therapeutic
interventions.
VOLUME04 ISSUE08
https://doi.org/10.55640/eijmrms-04-08-03
Pages: 25-30
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INTRODUCTION
Osteoarthritis of the hip is a multifactorial disease, with a variety of genetic and environmental factors
involved in its development. Some genetic mechanisms that contribute to joint cartilage damage and
the development of osteoarthritis include:
Genetic predisposition: Studies show that heredity plays an important role in the risk of developing
osteoarthritis. Genetic mutations that manifest in osteoarthritis, such as mutations in genes encoding
collagen (e.g., COL2A1), aggrecan, and other extracellular matrix proteins, have been identified.
COL2A1 gene: This gene encodes a type of collagen II, which is a major component of cartilage tissue.
Mutations in the COL2A1 gene can lead to impaired collagen structure and function, which in turn
affects the integrity and stability of cartilage tissue. This can accelerate cartilage damage, a key aspect
of osteoarthritis.
Collagen genes: Mutations in genes encoding different types of collagen can affect the strength and
elasticity of cartilage, making it more susceptible to damage and degeneration.
GDF5 gene: This gene encodes growth and differentiation factor 5, which is involved in the development
and maintenance of connective tissues. Mutations in this gene may increase the risk of developing
osteoarthritis. GDF5 is involved in the growth and development of bones and joints. Mutations or
genetic changes in GDF5 can interfere with normal joint development and contribute to the
development of osteoarthritis. This gene is also involved in tissue repair and regeneration processes,
so disrupting it can make it difficult for cartilage to naturally regenerate after damage.
These two genes, COL2A1 and GDF5, have attracted particular attention from researchers because they
play an important role in the structure and function of articular cartilage, as well as in bone remodelling
processes. Studying the role of these genes helps to understand the pathogenesis of osteoarthritis in
patients after COVID-
19. The COL2A1 gene encodes the α
-chain of type I collagen, which is a major
component of connective tissue and articular cartilage. Various polymorphisms of the COL2A1 gene are
associated with the risk of osteoarthritis and its progression. In one study, the COL2A1 gene
polymorphism (rs1800012) was associated with an increased risk of osteoarthritis. In addition, some
studies show an association between COL2A1 genetic variants and more severe clinical manifestations
of osteoarthritis, such as reduced articular cartilage thickness and osteophytes.
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The GDF5 (growth and differentiation factor 5) gene is a key regulator of joint and cartilage
development. Different genetic variants of GDF5 are associated with the risk of osteoarthritis and its
clinical manifestations. One study has shown that certain GDF5 polymorphisms are associated with an
increased risk of osteoarthritis. Other studies show an association between GDF5 genetic variants and
characteristics of osteoarthritis, such as the development of joint changes and the severity of clinical
symptoms. This confirms the role of GDF5 in the pathogenesis of osteoarthritis and its possible
influence on osteoarthritis characteristics in COVID-19 patients.
Studies on the role of COL2A1 and GDF5 genes in the characteristics of hip osteoarthritis in patients
after COVID-19 are relatively new and require additional studies to confirm and clarify the findings.
However, preliminary data indicate a possible influence of these genes on the risk of osteoarthritis and
its clinical manifestations in these patients.
To better understand the role of COL2A1 and GDF5 genes in the characteristics of osteoarthritis in
patients after COVID-19, further studies using large patient samples and different methods of genetic
variant analysis are needed. This will allow the development of more accurate approaches to diagnosis,
treatment and prognosis of osteoarthritis in a certain group of patients.
Genes regulating inflammation: inflammation plays a key role in the pathogenesis of osteoarthritis.
Alterations in genes involved in inflammatory processes, such as the interleukin or TNF-
α genes, may
contribute to the development of the disease.
Cartilage metabolism genes: Abnormalities in genes that regulate the synthesis and degradation of
cartilage components, such as matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), can lead
to imbalances in the maintenance of cartilage integrity.
FRZB gene: This gene encodes a protein that regulates bone growth and development by acting on
cartilage through WNT signaling pathways. Mutations in FRZB can contribute to cartilage abnormalities
and the development of osteoarthritis.
ADAMTS5 gene: This gene encodes an enzyme involved in the degradation of aggrecan, a major
component of cartilage.
IL1 and TNF genes: These genes encode inflammatory cytokines that may play a role in the pathogenesis
of osteoarthritis by promoting inflammation and cartilage destruction.
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Changes in genes related to div weight and height: Obesity is a significant risk factor for osteoarthritis,
so genes that affect div weight and metabolism (e.g. leptin genes) may also play a role in the
development of this condition.
Epigenetic changes: Specific mutations and epigenetic modifications such as DNA methylation and
histone modification can also influence the development of osteoarthritis.
Understanding the genetic factors that influence the development of osteoarthritis of the hip may lead
to innovations in the diagnosis and treatment of this disease in the future:
- Genetic research: it can help doctors identify patients at high risk of developing osteoarthritis before
symptoms appear. This will open up opportunities for early prevention, including lifestyle, dietary, and
physical activity changes that can slow or prevent the disease from developing.
- Medications targeting molecular targets: Medications designed to target different molecular targets
identified through genetic studies may be a new direction in the treatment of osteoarthritis. Such drugs
may include metalloproteinase inhibitors, agents that modulate neuronal signaling pathways, or
biologics that stimulate growth factors and cytokines.
- Developments in regenerative medicine: The use of stem cells and tissue engineering to repair
damaged cartilage can be improved using genetic information. For example, gene therapy can be used
to correct cartilage defects or stimulate cartilage regeneration at the molecular level.
- Disease biomarkers: Identifying biomarkers that may indicate osteoarthritis activity will allow
physicians to better monitor disease progression and treatment efficacy.
- Targeted nutritional supplements: Biologically active substances such as chondroitin, glucosamine, or
omega-3 fatty acids can be personalized based on a patient's genetic profile to improve joint health and
slow degenerative processes.
- Personalised exercise: Different types of exercise can be preferred based on the patient's genetic
profile to maximize the benefits of exercise and minimize the risk of joint damage.
- Personalised medication: Knowledge of genetic factors can help predict response to analgesics and
anti-inflammatory drugs, allowing individualization of pain management and management of side
effects.
CONCLUSION
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Thus, osteoarthritis of the hip is a complex, multifactorial condition influenced significantly by genetic
predispositions and environmental factors. Recent studies highlight the pivotal roles of specific genes,
particularly COL2A1 and GDF5, in cartilage integrity, joint development, and the overall progression of
osteoarthritis. Genetic variations in these genes have been associated with increased susceptibility to
the disease, its severity, and clinical manifestations, especially in patients following COVID-19.
Additionally, the involvement of other inflammatory and cartilage metabolism-related genes further
complicates the pathogenesis of hip osteoarthritis. Understanding these genetic factors offers
promising insights into the potential for early diagnosis, targeted therapies, and personalized medicine
strategies for osteoarthritis management, paving the way for advancements in prevention and
treatment protocols.
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