Features of the metabolism of connective tissue proteins. Regeneration of bone and cartilage tissue

Structure FunctionsCausesSymptomsTreatmentDrugs

Cartilage tissue is present in many organs, but it is subjected to the greatest stress in the joints. Cartilage covers the vulnerable areas of the bones in the joints and provides shock absorption, as well as resistance to stress, thanks to which we do not even think about what tests the joints face in the life of an ordinary person, not to mention the categories of people who subject their bodies to excessive stress. Unfortunately, cartilage can deteriorate over time for various reasons, leading to limited joint movement, pain and discomfort. Therefore, it is so important to take the necessary measures in time to restore the cartilage tissue of the joints.

Introduction

After studying this educational presentation, orthopedic traumatologists will have a clear understanding of the basic biochemical issues that relate to the characteristics of protein metabolism in connective tissue. This presentation will help you understand the role of different proteins for different types of connective tissue. Will clarify the understanding of the role of different types of collagens. Will provide basic knowledge about the synthesis and degradation of collagen and elastin. It is very important that this educational presentation will demonstrate the role of vitamins for metabolic processes in connective tissue. Of all the vitamins, it is especially important to note the role of vitamin C and cholecalciferol. This presentation will highlight the role of prolyl hydroxylase and lysyl oxidase in collagen and elastin metabolism. Also, after studying this presentation, orthopedic traumatologists will have a clear understanding of the stages of collagenogenesis and its regulation. Doctors of this profile will receive information about the remodeling and degradation of collagen and the basics of regeneration of bone and cartilage tissue.

What are the causes of destruction of cartilage tissue?

The main reason for the destruction of cartilage is a decrease in the quality of synovial fluid - a natural lubricant that protects the joint from excess friction and provides its nutrition. After all, there are no blood vessels in cartilage, but only “pores” that are saturated with joint lubricant. This means that degenerative processes in cartilage can be triggered by:

• insufficient production of joint lubrication
  (even with a physiologically normal volume of lubrication there may not be enough due to increased loads on the joint);
• lack of nutrients
  in the synovial fluid (for example, due to a poor diet or poor tissue nutrition);
• lack of conditions for the circulation of joint fluid
  (sedentary lifestyle, immobilization of a limb after injury) - after all, in order for it to wash the joint, it must be alternately in a state of loading and rest;
• insufficient consumption of clean drinking water
  and, as a result, chronic dehydration - cartilage, which is 70-80% water, loses its elasticity and begins to crack.

In case of injury, excessive stress without rest, or, less commonly, a systemic disease (metabolic or autoimmune), the nutrition of the periarticular tissues is disrupted. Due to inflammation, nutrients cease to flow normally into the synovial fluid, causing its production and quality to suffer, and the restoration of cartilage tissue slows down or stops. The cartilage is “starving”. When a limb is immobilized after an injury, there is no circulation of synovial fluid at all. Because of this, cartilage tissue loses its shock-absorbing properties and begins to deteriorate and become thinner. That is why, after an injury, it is important to correctly dose the load, receive proper anti-inflammatory treatment, drugs for the restoration of cartilage tissue and supportive therapy.

In addition to poor diet, physical inactivity and injury, cartilage destruction can be caused by:

• infectious diseases, especially chronic ones;
• endocrine disorders;
• chronic stress and lack of sleep;
• difficult working conditions;
• congenital or acquired anomalies of the musculoskeletal system;
• hypothermia or overheating;
• age-related changes;
• overweight;
• bad habits;
• genetic prerequisites.

Bone composition

• Bone and cartilage tissue are specialized types of connective tissue.
• Bone tissue is characterized by high mineralization (or calcification) of the intercellular matrix and contains by weight about 50% inorganic compounds, 25% organic compounds and 25% water.
• The bones contain 99% of the body's total calcium (in the form of hydroxyapatite: Ca10(PO4)6 (OH)2).
• Organic compounds in bone tissue are represented by proteins, lipids and heteropolysaccharides.
• The main share of organic substances is proteins (90% are collagen proteins).

Liquid connective tissue

Blood and lymph consist of cells and liquid intercellular substance (plasma). The formed elements of blood differ significantly in size and functions ( Fig. 5 ). Blood and lymph transport substances to organs and accept metabolic products that must be removed from the body.

Rice. 5. Adipose tissue. Blood

Blood functions:

• transport - transfer of oxygen and carbon dioxide;
• homeostasis - the constancy of the internal environment of the body;
• regulatory (humoral);
• •protective (immunity).

Bone matrix synthesis - osteoblasts

The synthesis of bone matrix is ​​carried out by osteoblasts (4-6% of all bone tissue cells) in two main stages:

1. Precipitation of organic matrix: Collagen proteins, mainly collagen type I, non-collagenous proteins (osteocalcin, osteonectin, BMP-2, osteopontin and proteoglycans, including decorin and biglycan) are secreted, which form the organic matrix.

2. Subsequent mineralization of the organic matrix, which occurs in two phases:

• vesicular (matrix vesicles are released from the apical membrane domain of osteoblasts; in them, sulfated proteoglycans immobilize calcium; if necessary, osteoblast enzymes destroy proteoglycans, and calcium is released through the Ca2+ channels of the vesicles, which are formed by annexin proteins),
• fibrillar.

Osteoclasts

Osteoclasts are notable for their structure and the presence of bone resorption enzymes:

• lysosomal H+-ATPase of the vacuole type,
• tartrate-resistant acid phosphatase,
• cathepsin K,
• matrix metalloproteinase-9 (MMP-9)

An increase in the number of osteoclasts and their activity (for example, during inflammation or metastasis) leads to osteoporosis or osteolysis.

Collagen and its types

Collagen is the main protein of connective tissue of multicellular organisms

• Collagen is the main insoluble fibrillar protein of connective tissue and extracellular matrix.
• The term “collagen” refers to a group of proteins that form a characteristic triple helix of three polypeptide chains.
• These proteins differ in size, function, and distribution in tissues.
• Currently, 28 types of collagen have been described.
• Types I, II, and III collagens are dominant in the human body, accounting for about 95% of all collagen types.

Type I collagen:

• found in bones, skin, tendons, ligaments, cornea, sclera, blood vessels;
• most abundant in the body;
• makes up 95% of various types of bone collagen 80% of all bone tissue proteins;
• heterotrimer: two α1 chains and one α2
• each chain consists of ~1000 amino acids;
• the length of this type of collagen is ~ 300 nm, and the thickness is 1-5 nm;
• consists of three domains: N-telopeptide, central three-helical domain and C-telopeptide;
• the central domain is represented by a repeating amino acid sequence: Glycine-X-U, where X is often proline, and Y is hydroxyproline;
• post-translational modification: hydroxylation (hydroxylation of lysine is especially important), glycosylation (can be enzymatic and non-enzymatic; non-enzymatic glycosylation intensifies with aging and leads to increased formation of advanced glycation products -AGEs);
• markers of bone matrix formation and antiresorptive therapy:
• N-terminal propeptide of type I procollagen (PINP), N-terminal propeptide of type I procollagen (used in clinical practice);
• C-terminal propeptide of type I procollagen (PICP).

• Markers of degradation and resorption:
• C-terminal (terminal) telopeptide of type I procollagen (CTX-1, β-CrossLaps) (used in clinical practice),
• neoepitope of type I collagen (C1M).

Type II collagen:

• found in cartilage, intervertebral discs, vitreous body;
• the Co12A1 gene is maximally expressed in the extracellular matrix and articular cartilage;
• three identical α1 chains, i.e. homotrimer;
• just like type I collagen, it forms fibrils approximately 300 nm in length and 1.5 nm in diameter;
• like all fibril-forming collagens, it is synthesized in the form of procollagen;
• The C-terminal propeptide is a non-collagenous domain (NC1) and consists of three identical chains;
• The N-terminal propeptide contains three domains: NC2, Col2, NC3; in osteoarthritis, the embryonic domain of N-propeptide, PIIBNP, is reexpressed (inhibits osteoclast survival and, accordingly, resorption);
• interacts with collagen types XI and IX and with small proteoglycans rich in leucine.

Type III collagen:

• found in the skin, vascular walls, lungs, liver, spleen;
• homotrimeric collagen (three α1 chains);
• participates in fibrillogenesis of type I collagen in the skin, cardiovascular system and intestines;
• bone morphogenetic protein 1 (BMP-1) is involved in the rate-limiting step of C-terminal peptide removal;
• Type III procollagen processing is increased in the presence of procollagen C proteinase enhancers (PCPEs). Identification and binding of PCPE is a promising target for antifibrotic therapy;
• “young” scar tissue contains mainly type III collagen and a small amount of type I collagen. However, with the “aging” of the scar, the ratio of collagen types I/III becomes 1/g. With keloids and hypertrophic scars, a predominance of type III collagen is noted;
• is a ligand for the G protein receptor (GPR56). This interaction determines the development of the cerebral cortex;
• also interacts with integrin α2β1 and von Willebrand factor, i.e. participates in adhesion and vascular regeneration.

Type IV collagen:

• found in basement membranes;
• contains repeating long (400 nm) helical regions that are interrupted by short non-helical fragments;
• the most flexible collagen, in 26 places its triple helix is ​​interrupted by a non-collagenous amino acid sequence;
• provides interaction between laminin, heparan sulfate, perlecan, nidogen, growth factors and cells;
• N- and C-terminal propeptides are not cleaved off and are the site of binding (cysteine ​​and lysine residues) during the formation of oligomeric forms of collagen;
• secreted by endothelial cells, epithelial cells, myocytes, adipocytes, etc.;
• contains various α-chains (α1-6);
• The N-terminal collagen domain (7S) is rich in cysteine ​​and lysine, there is a link between lysine and hydroxylysine, and is highly glycosylated, i.e. protected from the effects of collagenases;
• the central collagen domain contains about 1400 amino acid residues;
• The C-terminal globular domain (NC) contains a lot of methionine and lysine, which form a bond with each other;
• Goodpasture's syndrome and Alprot's syndrome are associated with autoimmune damage to the renal basement membranes (containing type IV collagen) and the development of glomerulonephritis.

Type V collagen:

• found in bones, cornea, lungs, placenta, along with type I collagen;
• minor long fibrillar collagen (390 nm);
• has a globular N-domain;
• collagen type V is necessary for fibrillation of collagen types I and III;
• collagen of this type binds to DNA, heparan sulfate, heparin, insulin, thrombospondin;
• heterotrimer: α12α2.

Type VI collagen:

• found in skin, cartilage, lungs, placenta, vascular wall, intervertebral discs, extracellular matrix;
• collagen, which forms microfibrils;
• short-chain collagen, has globular domains that are longer than collagen;
• laterally associated with type I collagen;
• two molecules form a dimer and then turn into a tetramer;
• contains a large number of Arg-Gly-Asp sequences, due to which it interacts with integrins and participates in cell adhesion (binds with fibroblasts, chondrocytes, hematopoietic and tumor cells);
• also binds to decorin, fibronectin, perlican, biglycan and tenascin;
• located next to the basement membrane;
• heterotrimer: α1α2α3;
• is an early sensor of the response to damage, regulates fibrogenesis and is responsible for intercellular interaction.

Type VII collagen:

• found in the skin (epidermal-dermal junction), oral mucosa;
• collagen, which forms “anchored fibrils”;
• synthesized by keratinocytes and fibroblasts;
• has a length of 450 nm;
• contains two terminal non-collagen domains and one central collagen domain;
• forms dimers by binding antiparallel to the non-collagenous N-terminal domain.

Type VIII collagen:

• found in endothelial cells, Descemet's membranes of the corneal endothelium;
• short chain collagen;
• the molecules of this collagen assemble antiparallel to form tetramers, forming hexagonal lattices, which ensure the transparency of the cornea.

Type IX collagen:

• found in cartilage, cornea;
• fibril-associated collagen;
• consists of three collagen (K, fibrillar) domains and four non-collagen (NC, globular) domains;
• antiparallelly attaches to type II collagen (limiting the size of fibrils) Lys-Lys bridges (K1, K2, NK1, NK2, NKZ);
• The HK4 domain is positively charged and is necessary for binding with hyaluronic acid or chondroitin sulfate during the organization of the intercellular matrix in cartilage;
• laterally associated with type II collagen.

Type X collagen:

• found in hypertrophied cartilage;
• normally constitutes 1% of the collagens of cartilage tissue;
• short chain collagen;
• like collagen types IV and VIII, collagen of this type forms network-like structures;
• homotrimer (consists of three α1 chains);
• binds calcium.

Type XI collagen:

• found in cartilage, vitreous body;
• minor collagen, which forms fibrils;
• heterotrimer (α1α2α3);
• a gene defect for this type of collagen leads to the development of:
• Stickler syndrome (a group of hereditary collagenopathies (types II, IX and XI of collagen, another name is hereditary arthrophthalmopathy. The disease is characterized by facial changes, eye damage, hearing loss and joint pathology),
• Marshall syndrome (hypoplasia of the midface, spondyloepiphyseal anomalies, cleft palate and sensorineural hearing loss, ectodermal dysplasia with hypertrichosis and hypohidrosis, thickening of the calvarial bones, hypertelorism).

Type XII collagen:

• found in skeletal muscles, skin, bones, tendons, ligaments;
• collagen associated with fibrils (stabilizes type I collagen);
• homotrimer (consists of three α1 chains);
• participates in the differentiation of osteoblasts and the formation of bone tissue, also regulates the polarity of fibroblasts;
• contains a large number of peptide sequences;
• Arg-Gly-Asp for binding to β1 integrin;
• disruption of the synthesis of this type of collagen leads to a decrease in the content of bone matrix proteins osteocalcin and osteopontin;
• a gene defect for this type of collagen leads to the development of Ehlers-Danlos syndrome, with clinically expressed joint hypermobility and muscle weakness.

What drugs do doctors recommend for restoring cartilage tissue?

Medicines for the restoration of joint cartilage tissue are produced in the form of tablets, capsules, sachets (powders), injections, ointments, gels and creams. What drugs are most effective for restoring cartilage tissue? Depends on the stage of the disease, the affected joint and the individual characteristics of the body. Injections have the highest bioavailability, but can be traumatic. Therefore, most patients prefer sachets and tablets.

Please note: all medications to restore cartilage tissue of the spine and joints must be taken long-term and systematically. The first noticeable improvements may appear only after several months of use - this is due to the slow metabolism of cartilage.

Chondroprotective drugs for restoration of joint cartilage tissue

To restore cartilage tissue, “building material” is needed - special proteins and natural polymers that ensure the strength and functionality of synovial cartilage. Since there are very few of them in the diet of a modern person, chondroprotectors come to the rescue to restore cartilage tissue.

These medications require lifelong use in long courses (from 3 months), but they are able to completely restore minor damage to the surface of the cartilage, facilitate recovery from injuries to cartilage tissue, slow down the progression of arthritis and arthrosis, and protect bones and joints.

The most convenient for restoring cartilage tissue are chondroprotectors in sachets - for example, Artracam

. The sachet contains a dose of powder for a single dose (this medicine for the restoration of cartilage tissue of the spine and joints is taken once a day). This is quite convenient, because... you don’t have to carry a whole blister, or even a bottle of pills, to work. At the same time, the bioavailability of glucosamine sulfate in artracam powder is 90-95%, practically not inferior to injections.

The following have proven themselves well as chondroprotectors for the restoration of cartilage tissue:

• artracs;
• structum;
• chondramin;
• chondroglucide;
• movex;
• arthra chondroitin;
• artradol;
• chondroguard.

These drugs for the restoration of cartilage tissue can be used not only for treatment, but also for prevention.

Metabolism correctors and homeopathic medicines for restoration of joint cartilage tissue

The pharmaceutical group of homeopathic remedies includes drugs for the restoration of cartilage tissue with both proven and unproven effectiveness. Therefore, the choice of these drugs should be approached carefully, focusing on the doctor’s recommendations. Of greatest interest for the restoration of cartilage tissue are bioregulatory anti-inflammatory and relaxing agents of plant, animal and mineral origin, as well as external warming and locally irritating drugs.

• traumeel (lozenges and gel);
• target T (tablets);
• bischofite (compresses);
• tinctures and ointments based on the fruits of capsicum;
• Horsepower for joints (balm);
• toad stone (balm with toad extract).

Correctors of the metabolism of cartilage and bone tissue, in addition to chondroprotectors based on glucosamine and chondroitin sulfate, also include such reparative drugs as:

• piascledine;
• adgelon;
• vitreous body;
• Super Calcium;
• tridin;
• alendronic acid preparations (for example, osterepar);
• others.

These medications for restoring cartilage tissue of the spine and joints do not replace full-fledged therapy.

Angioprotective drugs for restoration of cartilage tissue

Angioprotectors and blood microcirculation correctors strengthen capillary walls, improve nutrition and restoration of cartilage tissue. Everyone knows that there are no blood vessels in the cartilage itself. However, their dense network permeates the perichondrium (perichondrium), which is responsible for the division of chondrocytes, growth and repair of cartilage tissue in case of damage. It is from the blood of the perichondrium that it receives the nutrients so necessary for the restoration of the cartilage tissue of the joints.

It is also important to strengthen the circulatory system to avoid fragility of blood vessels and hemorrhages into the joint cavity. A capillary rupture can cause even a harmless, at first glance, bruise. And with blood, infectious pathogens can enter the joint and begin to destroy cartilage tissue. This is especially dangerous for those patients who suffer from chronic foci of infection in the body - tonsillitis, caries, cholecystitis, rhinosinusitis, intestinal dysbiosis and others.

Therefore, as auxiliary drugs for the restoration of joint cartilage tissue, doctors prescribe:

• pentoxifylline (trental);
• horse chestnut extract (aescusan);
• troxerutin;
• troxevasin;
• cinnarizine;
• Detralex;
• angionorm;
• Cavinton;
• betahistine (tagista).

Synovial Fluid Prostheses

If pockets of erosion have already appeared on the cartilage, and there is not enough synovial fluid in the joint, lubricating prostheses are required for normal sliding of the cartilage. They allow the surface of the cartilage to rest and recover. Such drugs for restoring joint cartilage tissue are injected directly into the articular capsule of each affected joint. They are used primarily for the treatment of large joints. Replacement drugs for the restoration of joint cartilage tissue include:

• synvisc;
• fermatron;
• sinochrome;
• suplasin;
• ripart;
• Duralan;
• giruana;
• hyalrepayer.

Implantation of autologous chondrocytes

• More recent approaches to cartilage regeneration include autologous chondrocyte implantation (ACI) and now matrix-associated chondrocyte implantation (MACI), as well as autologous matrix-induced chondrogenesis (AMIC).
• MACI is a two-step procedure (and an advance on the original ACI procedure) in which healthy cartilage cells are collected from the patient, expanded, seeded into a collagen matrix, and then re-implanted into the cartilage defect. AMIC, on the other hand, is a one-step procedure in which an acellular collagen matrix is ​​implanted into the cartilage defect.
• TGF-B1 (transduced allogeneic chondrocytes (Invossa), intra-articular injection) demonstrated a high hyaline cartilage proliferation index.

Platelet Rich Plasma (PRP) Therapy

• PRP modulates the inflammatory and catabolic environment through a locally applied concentrate of platelets, leukocytes and growth factors (platelet-derived growth factor - PDGF, fibroblast growth factor - FGF, hepatocyte growth factor - HGF).
• Recent efforts have focused on optimizing delivery methods that allow platelets to slowly degranulate their biological constituents, which may promote healing and improve osteoarthritis symptoms over a longer period of time.
• There are various factors that influence the progression of osteoarthritis in the joints, including inhibition of inflammatory cytokines and changes in enzyme expression levels.
• PRP therapy aims to mediate inflammatory and catabolic factors in the degenerative environment through the secretion of anti-inflammatory factors and chemotactic effects, as well as increasing the synthesis of type II collagen and cortical aggrecan protein.
• There is a growing number of studies that have demonstrated the clinical benefit of PRP for the non-operative treatment of osteoarthritis.
• Additional randomized controlled trials with long-term follow-up are needed to confirm the therapeutic efficacy of PRP in these settings.
• Additionally, further basic research as well as carefully designed preclinical studies and reporting standards are needed to clarify the effectiveness of PRP for cartilage repair and regeneration for future clinical applications.

Stromal Vascular Fraction (SVF) Therapy

• SVF therapy (from the English Stromal Vascular Fraction) is treatment with stromal vascular fraction (SVF) cells obtained from one’s own (autologous) adipose tissue.
• SVF cells are injected intra-articularly under local anesthesia.
• The goal of SVF treatment is to relieve joint pain and restore articular cartilage.
• Clinical observations of the use of this option for stimulating the regeneration of hyaline cartilage demonstrate high efficiency in patients with stage 11-111 osteoarthrosis deformans (Shevela E.Yu. et al., 2017).

Treatment

Mostly surgical. For this purpose, doctors use:

• radical surgical treatment (resection of chondroma within intact tissues with possible subsequent plastic surgery);
• endoscopic removal (for example, removal through endonasal access of intracranial chondroma) is a less traumatic method with faster rehabilitation of patients;
• radiation therapy (used for chondromas of the skull base before and after their removal or in inoperable situations, it helps to destroy the remaining chondroma cells);
• stereotactic radiosurgery (elimination of chondromas with a radiation cyber knife or gamma knife that does not affect healthy tissue).

Use of growth factors

• Results from preclinical testing of BMP-2: Dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone restoration, greater bone growth at the defect margins, and lower specific bone surface area than single delivery of IGF-1.
• Result of preclinical testing of BMP-7: Controlled supplementation of BMP-7 can improve the chondrogenic effect of TGF-r3, and scaffolds loaded with this combination of growth factors can induce cartilage formation in human mesenchymal stem cell cultures.
• Clinical trial result for FGF-18 (sprifermin): qMRI showed an increase in cartilage thickness in a dose-dependent manner in patients with knee osteoarthritis with an acceptable safety profile after 3 years.

How to start the restoration of cartilage tissue in joints?

If treatment is started in a timely manner, conservative methods of restoring cartilage tissue of joints are used. These include:

• treatment with chondroprotectors;
• massage (classical therapeutic, hydromassage, lymphatic drainage, vacuum, self-massage);
• physiotherapy;
• taking vitamins (at least 2 times a year, in the autumn-spring period), homeopathic remedies and blood microcirculation correctors;
• swimming;
• physiotherapy;
• injection therapy (intra-articular administration of hyaluronic acid, platelet-rich plasma, Orthokine);
• use of orthoses (orthopedic bandages, corsets, insoles, as well as orthopedic furniture, backpacks, etc.).

It is also important to eliminate habits that increase its destruction:

• addiction to tobacco and alcohol;
• excessive consumption of coffee (especially decaffeinated);
• overeating or eating 1-2 times a day;
• lack of sleep;
• penchant for sweet and salty foods;
• self-treatment of infectious diseases and injuries;
• excessive exercise;
• the habit of dressing inappropriately for the weather.

If the cartilage is not subject to natural restoration, in addition to taking chondroprotectors to restore cartilage tissue, surgical treatment is recommended - for example, arthroscopic debridement (cleaning and polishing of cartilage), arthroscopic microfracture (creating holes for blood flow with growth factors), osteochondral transplantation (transplantation of cartilage of a patient from an unloaded area of ​​the joint), transplantation of cultures of chondrocytes grown in the laboratory from a fragment of healthy cartilage, and others.

Removal of neighboring senescent cells (senescent)

• A recent study by Jeon et al found that senescent chondrocytes accumulate around traumatic cartilage injuries and are associated with the development of arthritis.
• Clearing these senescent cells through intra-articular injection of a senolytic molecule attenuated the development of arthritis in a mouse model.
• Another recent study showed that rejuvenation of aged MSCs with SRT1720, an activator of SIRT1, significantly improved cardiac function and angiogenesis in a Ml rat model compared to control MSCs.
• These potential therapeutics aimed at rejuvenating, optimizing, and recruiting endogenous stem cells are likely to improve the effectiveness of cartilage tissue engineering techniques in elderly patients.

What are the consequences of the destruction of cartilage tissue?

The loss of hyaline cartilage and, as a result, freedom of movement in the joint, is associated with changes in the density and elasticity of cartilage tissue. The consequence of this process is arthritis, arthrosis and other degenerative-dystrophic diseases of the musculoskeletal system, which require lifelong medication to restore the cartilage tissue of the joints.

When the cartilage lining thins, the joint begins to deform and take on an unnatural position. Bones and adjacent tissues are injured and rub against each other, leading to inflammation, the appearance of microcracks and bone outgrowths.

Damage or wear of cartilage leads to:

• reduction in the range of motion in the joint (for example, the arm does not bend completely);
• severe pain that may not subside even at rest and worsens “in the weather” or after physical activity
• chronic inflammatory process with deterioration of sleep and appetite, loss of muscle mass due to atrophy, decreased immunity;
• in advanced cases, complete contracture with joint fusion is possible, as well as disability, when the patient cannot take care of himself even at home;
• deterioration in the quality of life and emotional status of the patient due to pain and limitations in mobility.

Since cartilage tissue is practically incapable of self-healing, even minor damage must be treated immediately - for example, by taking chondroprotectors to restore cartilage tissue. Otherwise, erosion will worsen until the cartilage is completely abraded and the bone surface is exposed.