Osteoarthritis (OA) is a disease with an increasing incidence as age advances. Patients typically experience pain, and in severe cases, it can lead to disability. Currently, the treatment options for OA are quite limited, primarily focusing on pain relief and anti-inflammatory measures, which are insufficient for preventing and slowing the progression of the disease. Research has shown that a hormone called Osteoglycin (OGN) is significantly reduced in the chondrocytes of OA patients, potentially affecting the homeostasis of their cartilage cells (Leong, 2018). Our project aims to validate the feasibility of OGN as a potential therapeutic target for OA. In order to assess the real-world value and significance of our project, interviews were conducted with three experts, and an online survey was carried out.
We designed this questionnaire to investigate the current demand for osteoarticular synthetic drugs, the impact of osteoarthritis drugs, and the public understanding of the principles and effects of the products.
Figure 1. Sex
In the initial inquiry, we sought to ascertain the biological sex of the participants in order to examine whether any disparities in sex were associated with variations in the occurrence of osteoarthritis, in conjunction with the subsequent inquiry. The aforementioned findings reveal that 53.9% of the participants identified as male, while 46.1% identified as female.
Figure 2. Age
In the second question, we asked the biological age of the respondents to see if the difference in age had an effect on the prevalence of osteoarthritis in conjunction with the next question. The results are shown in the figure above, which shows that 71.53% of the participants are between 55 and 65 years old, while the minimum for young people under 45 years old is 2.03%.
Figure 3. Status of illness
In the third question, we asked the respondents if they had been diagnosed with osteoarthritis, in order to combine the two questions above to see if the difference in age and gender had an effect on the prevalence of osteoarthritis and our target population. The results are shown above and its show that 22.37% of the people who answered our questionnaire suffered from osteoarthritis while 77.63% of the respondents did not suffer from osteoarthritis.
Figure 4. Diseased parts
According to the figure, for the multiple-choice question on diseased parts, there were 55 valid fillers. Among them, the knee is the most common diseased part, with 46 people choosing it, accounting for 83.64%. This was followed by the spine, which was selected by 13 people, accounting for 23.64%. Fingers and hips had the same number of selections, each with 10 selections, accounting for 18.18%.
The analysis of the data shows that the knee is the most frequently selected diseased part, which may be related to the higher pressure on the knee in daily life. The spine is also a common diseased part, which may be related to long-term sitting or poor postural habits. Fingers and hips were chosen equally often, possibly because these two areas are also prone to injury or disease. It should be noted that due to the small sample size of the data, there may be some bias in the analysis results and there may not be representative of the overall population. For the other parts of the body, the number of choices was 0. This may be because no one in the sample chose that option, or the result may be due to insufficient sample size. The size and representativeness of the sample must be taken into account in further analysis.
Figure 5. Duration of illness
As shown in the figure, 41.82% of patients with osteoarthritis have been suffering for more than three years, while patients who have just become ill are very few and only 18.18%.
Figure 6. Treatments
According to the figure, external medication and acupuncture had the same percentage of 38.18% and were the most popular treatments among the subjects. The percentage of oral drug treatment was 14.55% and the percentage of surgical treatment was 9.09%. Therefore, topical medication and acupuncture were the most popular treatments, while surgery was less popular. This may be due to the fact that people are worried about surgery.
Figure 7. Condition after treatment
Through this figure, we found that 61.82% of patients feel improved after receiving treatment, but there are still 25.45% of patients, who think there is no effect, and patients who think that significant improvement only accounts for 12.73% of all people, it can be seen that most patients, the effectiveness of the current market drugs is not very satisfied, so once our new synthetic drugs are successfully developed, they are likely to capture a significant market share, due to the combination of various favorable factors such as economy and convenience.
Figure 8. Causes of disease
Frequent climbing and descending of stairs was voted the most joint damaging habit, accounting for 63.39% of the total effective number of times. This may be due to the fact that walking up and down stairs puts more pressure on the knee and ankle joints, which can easily lead to joint wear and damage in the long run. Sports such as badminton and mountaineering were chosen as the most damaging joint habit, accounting for 47,12% of the total valid counts. This may be because these sports can put pressure on the joints. Repetitive impacts and twisting are performed, which can easily lead to joint damage. Sitting and standing for a long time was chosen as the most damaging habit, accounting for 54.24%. Prolonged sitting or standing can lead to joint stiffness and poor blood circulation, increasing the risk of joint pain and inflammation. Occupational diseases were chosen as the most joint damaging habit with 48.81% of the total valid counts. This may be due to the fact that certain occupations require long periods of time in specific positions or performing repetitive motions that cause joint damage. Other habits were selected as the most injurious habits, accounting for 11.53% of the total valid counts. This may be due to the fact that there are other habits or factors that can cause damage to the joints that are not specifically listed in this data. To summarize, frequent going up and down stairs, sports, sedentary standing and occupational diseases are the habits that hurt joints the most. In our daily life, we should pay attention to avoid these habits to protect the health of our joints.
In the ever-evolving field of synthetic biology, where innovation is at its core, understanding its implications and applications is crucial. To delve deeper into this exciting realm, we had the privilege of interviewing some renowned experts in synthetic biology and a pioneer in the osteoarthritis field. Our aim was to shed light on the significance of synthetic biology and its real-world applications.
Interview with Dr. Wang Dongfeng
Purpose of the Interview:
The primary objective of this interview was to gain insights from the expert who has been instrumental in shaping the field of synthetic biology and osteoarthritis. We aimed to explore the multifaceted dimensions of synthetic biology, its relevance in modern science, and the potential it holds for addressing critical global challenges.
On August 11th, we had an online interview with Dr. Wang Dongfeng to learn about the causes and symptoms of osteoarthritis from a professional point of view, as well as to provide us with a professional opinion on the feasibility of the project's goals. Dr. Wang Dongfeng is a university lecturer and an Associate Chief Physician. He holds a Ph.D. in Orthopedics from Wuhan University and works at Wuhan University People's Hospital (Hubei Provincial People's Hospital) in the Department of Emergency Surgery. His expertise lies in various surgical emergencies, with a particular focus on the diagnosis and treatment of fractures, joint injuries, acute and chronic arthritis, as well as burns.
Record of Interview：
Part A. Professional understanding of osteoarthritis
i. The definition of osteoarthritis
Dr. Wang mentioned that osteoarthritis is actually a form of degenerative arthritis, which is wear and tear of the joints, and degeneration exposes the joints to synovial fluid in the joint cavity. It causes joint pain, stiffness and interference with normal activities.
ii. What factors increase a patient's risk of developing osteoarthritis?
Osteoarthritis is caused by a combination of factors, such as the individual's metabolic level, and a decrease in the cartilage matrix. Or age-related degeneration of the joints, as the cross-sectional area of the joints remains constant and the pressure on the joints increases due to overweight. Or excessive sports and special labor postures and other reasons. The combination of these causes leads to the development of osteoarthritis. Or because of uneven joint fractures, accessory cruciate or anterior and posterior cruciate ligament injuries, meniscus injuries and other reasons. The environment in which a person lives is too high in humidity or too low in temperature reducing blood circulation and making cartilage cell recovery difficult. Genetic factors also play a role and, the older the person gets, the risk of developing the disease is further increased with it.
Part B. Disease and related conditions Understanding current treatments for osteoarthritis
i. The vast majority of patients prefer medication, is this choice made because of better efficacy or is it more of an economic consideration?
Patients will be in a position to worry about the trauma of surgery such as the uncertainty of anesthesia and surgery because the drugs are cheaper and also in a position to worry about the trauma of surgery such as anesthesia and surgery. At present, for the treatment of mild osteoarthritis, there are two kinds of treatment, one is a little conservative drug treatment, more popular with patients, we learned from Dr. Wang, the reason is that this kind of drug treatment is more affordable, and some patients are a little worried about the problems of the operation, so the majority of people, choose the drug treatment.
ii. What are some other non-drug treatments for people with mild osteoarthritis? How can they help relieve symptoms?
Patients may consider taking aspirin or milder non-steroidal anti-inflammatory drugs. Or take a joint cavity injection of sodium vitrate, tretinoin can reduce the local inflammatory response it can reduce the local inflammatory response, it is a long-acting hormone. It's a long-acting hormone. It's a hormone that reduces the local inflammatory response, but it has a disadvantage in that it inhibits glucocorticoids, which inhibit chondrocyte synthesis, and it reduces metabolism. This drug is effective for a short period of time. It's not really appropriate for the ultimate treatment. Arthroscopic surgery flushes the inflammatory factors in the joint with saline and creates microfractures or drills holes in the broken surface to allow stem cells in the bone marrow to promote repair.
iii. Does a combination of Western and Chinese medicine help patients recover faster?
Dr. Wang showed that the combination of Chinese and Western medicine is beneficial for joint osteoarthritis treatment. Chinese medicine, in particular, utilizes heat therapy and acupuncture, which can enhance the flow of qi and blood, promoting cartilage repair. Patients can also take preparations that invigorate blood and vitalize qi, including herbs such as astragalus, angelica, Sichuan hyssop, and panax ginseng. This can promote the operation of qi and blood and increase local metabolism.
iv. Are there novel treatments in the current academic field?
Dr. Wang mentioned that macrophage-targeted drugs don't have enough data on their effect yet, the sample size of the data is not large enough. Dr. Wang does not believe that this drug can have a significant effect at this time.
Part C. Common Problems and Dilemmas Understanding the Feasibility of Project Objectives and Obtaining Professional Advice
i. Have hospitals previously collaborated with pharmaceutical companies, and if so, what has been the nature of their cooperation?
The cooperation between hospitals and pharmaceutical companies is limited to the efficacy of the drugs, the adverse effects of the drugs, and the allergic reactions to the drugs. Hospitals give them feedback, and drug companies adjust drugs based on that feedback. This is the case with the withdrawal and elimination of some drugs that don't work.
ii. How can clinical teams in a general hospital be better coordinated to provide efficient care when dealing with patients with osteoarthritis?
Dr. Wang said the hospital will be based on the patient's condition in strict accordance with the principles of treatment to develop a treatment plan which, at the same time, the hospital will take into account the patient himself. Consider his expectations and economic conditions. Provide each patient is individualized medical services.
iii. What direction will the treatment of osteoarthritis take in the future?
First, for mild to moderate patients, joint injections and arthroscopic localized medication will be used. Combined with Chinese medicine to promote local blood circulation, which is called qi and blood running in Chinese medicine, to repair the joint cartilage as much as possible in order to achieve a good therapeutic effect. For severe patients. Individualized artificial joint replacement surgery can be used, according to the size, thickness and contour of his personal bones. Using 3D printing, print out the hip or knee joint that each person needs to replace. The result of the surgery will be a better possibility. It will also improve the mobility of the joint after the surgery and reduce the pain. If the mobility of the joint is basically fine, then the surgery is quite successful.
vi. Of the currently available medications for the treatment of osteoarthritis, which ones are most effective for patients? Is it possible that osteosynthetics may be more effective in comparison?
Dr. Wang said osteoglycans are a necessary component of cartilage matrix synthesis, a necessary component of cartilage mechanism synthesis. But it may not be effective for every patient. There are certain limitations, for example, some patients have more difficulty absorbing the drug with the gastrointestinal, resulting in less effective results. Or in the digestive process, the drug in the stomach and hydrochloric acid, in the small intestine and bile may lead to the decomposition of these drugs, if decomposed, even if it can reach the joint cavity, may not play a significant role. Therefore, Dr. Wang personally believes that it is best to use the injectable form of the drug. Directly into the joint cavity. Another way is to make the drug slow-release. Under the guidance of arthroscopic surgery, it can be fixed directly into the cartilage defect. It has rough cancellous bone on it that can be embedded. Osteoglycans can be made to adhere directly to it if it is relatively slightly softer. Or take other fixation anchored to the surface of the defect in the cartilage will also achieve better results. Using an arthroscope to create a microfracture or drill a hole in the defect to allow stem cells to flow down into the bone marrow. A sample of the patient's own platelet-rich blood is injected into the joint cavity. It provides a growth factor that catalyzes the reaction between the cartilage and the stem cells and the osteoglycans. It can promote the repair of this cartilage matrix and chondrocytes, which ultimately promotes the efficacy of osteoglycin.
v. Recommendations on drugs in clinical trials
Dr. Wang also recommended that if you need to conduct medical experiments on living organisms, it is recommended to start with animals like pigs because their bone and joints are the most similar to the human body, with the same meniscus, anterior and posterior cruciate ligaments, and joints. Moreover, they can satisfy the characteristics of larger body weight but thinner joints. You can use an arthroscope to cut through some of the cartilage and then cut the meniscus open. In this way let the animal walk with the injury for a while. Then the animal model can be manufactured efficiently.
Figure 9. Expert interview
Interview with Dr. Guo Lei
We interviewed Dr. Guo Lei, who used to be a dedicated researcher and a Postdoctoral Fellow at the National University of Singapore. She is also an M.S. supervisor in her field of expertise. Dr. Guo is affiliated with Ruijin Hospital, Shanghai Jiaotong University School of Medicine, and the Shanghai Institute of Orthopaedics and Traumatology. Her primary area of research focuses on investigating the role and mechanisms of non-coding RNAs in the context of bone and joint degenerative diseases.
The primary objectives of this interview are as follows.
A. To understand the causes of osteoarthritis from a professional point of view.
B. To understand the current treatment of osteoarthritis diseases and related conditions.
C. To understand the feasibility, common problems and dilemmas of the project objectives, to obtain professional opinions.
Figure 10. Expert interview
Here are the core contents of this interview.
Part A. Understanding the causes of osteoarthritis from a professional point of view
1. What are the main causes/factors of osteoarthritis?
Biologically, the main cause of osteoarthritis is actually the wear and tear of the cartilage surfaces of the joints. This can be caused by a number of factors:
l Aging factor: aging can cause a degenerative change, which can cause a state of articular cartilage degeneration. That's why older people are more likely to get osteoarthritis.
l Physical factor: obese and overweight people also have a much higher probability of getting osteoarthritis than ordinary people since their weight adds more pressure onto their cartilages.
l Illness factor: people who have gout and rheumatoid arthritis, have been reported with a higher probability of osteoarthritis development.
l Movement factor: people who are required to do repetitive joint weight-bearing tasks over a long period of time (e.g., construction site workers), may often experience wear and tear on the cartilage surfaces of the joints, which may also increase the risk of developing osteoarthritis.
l Genetic factor: the general appearance of osteoarthritis and racial inheritance have a certain relationship, generally speaking, osteoarthritis patients will be detected with the family incidence rate and increase.
2. What are the cells or what are the germs that cause osteoarthritis from the internal perspective of the body?
Osteoarthritis is a sterile inflammatory condition, it is not the kind of inflammation caused by a bacterial infection as commonly understood. The types of cells that occur in osteoarthritis are very diverse. This includes things like chondrocytes, which are the only type of cellular tissue on the cartilage surface. There are also synoviocytes, which are the synovial cells inside the synovial tissue inside the joint capsule. The synoviocytes produce inflammatory factors, and the inflammatory factors act on the surface of the cartilage, causing an inflammatory response in the chondrocytes, which biologically destroys the cartilage surface of the joint. Again, the subchondral bone is mainly involved in the production of sclerotic osteoid in the subchondral bone, and the cells involved in that include osteoblasts, osteoclasts, and the addition of neovascularization, which at this time involves the endothelial cells of the blood vessels. Although this disease is called osteoarthritis, it is not caused by mere factors. It is a combination of interactions between various tissues in the joint cavity.
3. What is the progression of osteoarthritis?
Generally speaking, osteoarthritis is divided into four stages, the first stage is the pre-arthritic stage. In this stage, there have not yet formed any obvious pathological changes. The patient usually has no symptoms, or only a mild symptom, such as mild joint pain. At this point, if the patient takes timely measures, it can slow down the development of the disease. Progressing further, it’s the early of arthritis. At this stage, the patient will experience pain, stiffness and discomfort in the joints at aggravation. Arthritis at this stage will affect the daily activities of patients for a bit. But if you can still actively progress in targeted treatment, it may relieve the symptoms and slow down the condition of arthritis. Then further down the room show is the middle stage. At this stage, the pain and stiffness in the joints will feel very serious at a persistent state. The joint will also experience redness, swelling and inflammation. Arthritis at this stage will obviously affect the daily life of a person, people who have arthritis at this stage cannot go up and down the stairs or do laundries. The last stage is the advanced stage, in which the pain and stiffness of the joints completely affect the patient's daily life, and the patient cannot walk normally, which is equivalent to disability.
Part B. Disease and related conditions- understanding current treatments for osteoarthritis
1. What are the main treatments available for osteoarthritis? What are the cons of these treatments?
Osteoarthritis is currently curable with surgery because it is not yet like other diseases. For other diseases, the effect may not be so obvious, such as tumors, tumors can not be eradicated. However, in the case of osteoarthritis, if joint replacement surgery is performed at the most advanced stage, the result is very good, and many people can even continue to play sports again. However, there are two disadvantages of the surgery, because the prosthesis is a foreign body, so it will cause immune rejection to some organisms. Then there is the time it takes for this surgery to heal. In the past, we used imported materials, put in, its life expectancy material life expectancy may only be ten years 20 years, and now the country developed its own materials, it may have a relatively short life expectancy. And once the prosthesis is put in, put in, after a long time, it will be loose, it will form a sterile inflammation. Of course it has to be very long, not that put in, immediately will have this reaction is a number of years later there are many people is put in, may not have this symptom for the rest of their lives, it is only a small probability of events.
Part C. Common Problems and Dilemmas and Feasibility of Project Objectives, and Obtaining Professional Advice
1. Our project aims to investigate into the effect of OGN in catalyzing chondrocytes to treat or alleviate osteoarthritis, what do you think about the feasibility of this project?
There are few studies on osteoglycans in the treatment and relief of osteoarthritis. Further validation is actually needed for its feasibility. It needs clinical validation and biological research validation. Osteoglycans are proteins secreted by mature osteoblasts, which themselves have a very good role in bone metabolism and promoting bone formation. And there is some literature that says that it has a repair ability for chondrocytes and can improve the stability of cartilage tissue. But it's true that right now there is no application for osteoglycans in osteoarthritis, so it's not impossible for us in this project, if the final study can identify a protective mechanism of osteoglycans on cartilage, to develop some new drugs based on this later. Our team is able to provide a target for drug companies to show them that this path is possible and can be traveled to produce drugs based on it. Overall, osteoglycans may be able to have some effect on osteoarthritic relief, but this still needs to be verified, you can't say it's not feasible. All scientific research is done from a situation where people don't know if it's feasible or not. But if do not try, then it is certainly not feasible.
2. If we were to say that we succeeded in researching osteosynthesis application in treating arthritis, what kind of uncontrollable side effects or other aspects of it might there be?
It is possible that this medicine is not good for the heart, osteosynthesis it can cause an enlargement of one of the ventricles when used in excess, which is not good for the heart. The rest of the side effects are to be determined because it has not been used in orthopedics. But the side effects are also due to the dosage.
3. Among other medications, what is usually used to overcome these side effects of a drug?
First of all, in order to avoid side effects you need to know the patient's underlying condition and allergies. Secondly, in order to avoid the side effects of the drug you need to get the dosage right and warn the patient about the precautions. Because some patients have gastrointestinal lesions (e.g., ulcers), or some patients with liver disease, you need to remind him of these drugs, which will have some gastrointestinal side effects, he may not be able to use. There are also some cardiovascular patients with cardiovascular disease, they themselves with cardiovascular disease drugs is to relieve pain, while using drugs containing osteosynthesis will increase the risk of heart attack and stroke. There are also patients with poor renal function, this drug you can not give him to use, after the use of his own poisoning. The main thing is that you need to know whether the patient has any other underlying diseases, that does not have these underlying diseases, then in accordance with the normal amount of use is generally no problem.
4. So, since glutathione is a very new concept, can we not assume that the successful results of our scientific research, if any, are having some positive impact on the scientific community?
That's for sure. Every new discovery you make has its own value. But as to whether or not these discoveries eventually make it to the clinic, it's a very long process, not just 3 or 5 days or 3 or 5 months. The development cycle of a drug, from the time you start developing it to the time it finally makes it to the clinic, like it's available to the patient is probably going to be ten to fifteen years. You can only provide some ideas to the company that is doing these drugs, and maybe the drug company will address the point that you provide, and he's going to involve some peptides, or he's going to involve some molecular drugs. He just intervenes to that point. Really wants to step into the clinical world, the patient really can use the time, the time to ten to fifteen years, and he invested in this funding and may also want to be in the hundreds of millions of dollars of this degree. So there's still a long way to go.
Interview with Dr. Zhu Wen
In our quest to delve deeper into the realm of Bone Glucosin, we had the honor of interviewing Dr. Zhu Wen, a distinguished expert in rheumatism research within the Department of Traditional Chinese Medicine at the First Clinical Medical College of Nanjing University of Traditional Chinese Medicine. Our aim was to gain valuable insights into the significance of Bone Glucosin and its potential implications for our project in the International Bioengineering Competition.
Dr. Zhu provided us with a comprehensive understanding of Bone Glucosin, highlighting its significance in rheumatism research. He explained that Bone Glucosin, a natural compound found in certain herbs, has shown promising results in promoting bone and joint health. It possesses anti-inflammatory properties and the potential to slow down the degenerative processes associated with conditions like osteoarthritis.
He emphasized that ongoing research in traditional Chinese medicine is focusing on harnessing the therapeutic potential of Bone Glucosin. Preliminary studies suggest that it can alleviate joint pain, reduce inflammation, and enhance overall joint function.
The following are fundamental recommendations given to us by Dr. Zhu:
Redefining our Approach: The insights from Dr. Zhu have reshaped our perspective on Bone Glucosin. We now recognize its potential as a valuable component in our project's approach to addressing osteoarthritis.
Integration of Traditional Chinese Medicine: Dr. Zhu's expertise underscores the importance of integrating traditional Chinese medicine practices into our project. This holistic approach may offer a more comprehensive solution for managing rheumatism-related conditions.
Future Collaborations: We see the possibility of collaborating with experts like Dr. Zhu in the future to explore the full potential of Bone Glucosin and ensure that our project aligns with the latest advancements in the field.
The interview with Dr. Zhu Wen has significantly enriched our project's human practice aspect. It has reinforced our commitment to incorporating traditional Chinese medicine principles and exploring the therapeutic potential of Bone Glucosin in managing osteoarthritis. We now have a deeper understanding of how our project can contribute to the broader field of rheumatism research and potentially improve the lives of individuals affected by these conditions.
Figure 11-12. Expert interview
In summary, our interviews with these experts and the questionnaire survey have provided us with valuable insights into Osteoarthritis (OA) and Osteoglycin (OGN). We have gathered a wealth of firsthand data through these interactions. This also prompts us to consider the integration of Traditional Chinese Medicine. Additionally, this experience offered an intriguing glimpse into the realm of synthetic biology. It emphasized the pivotal role of this field in shaping the future of scientific research and its potential to address some of the most pressing global challenges. As synthetic biology continues its advancement, it is of utmost importance that we actively engage in thoughtful discussions and ethical considerations to ensure its responsible and advantageous application.
Our end users include Pharmaceutical Giants, Mid-Sized Enterprises, and Niche Market Participants.
We experimentally verified that OGN can be used as a new target for OA therapeutic drugsand provide targets for screening drug companies to develop better OA therapeutic drugs withthis target. As a validation of the research to develop new targets for better OA therapeuticdrugs, our experiments are at the upstream stage of the entire drug production chain,providing pharmaceutical companies with one of the most critical targets for midstream R&D.
In the real world, we plan to realize it through diverse channels, including broadcast media, print media, digital advertising, and social media.
Leong I. Osteoglycin-linking bone and energy homeostasis. Nat Rev Endocrinol. 2018 Jul; 14(7):379.