Inflammation is regenerative medicine for subchondral bone

New research from doctors in China appears in the June 2017 edition of the medical journal Osteoarthritis and cartilage.It centers around the relationship between stromal cell-derived factor-1 (SDF-1) in regulating subchondral bone changes during the progression of osteoarthritis.

What are the doctors looking for? The role of inflammation in creating bone spurs and how regulating stem cells can prevent it.

Stromal cell-derived factor-1 (SDF-1) are part of a family of small proteins (Chemokines) that provide communication and direction to injury stimulus. These cells play an important role in sending messages to mesenchymal stem cells that the stem cells should initiate the process of differentiating (changing) into osteoblastic cells, (the creation of new bone.)

What the Chinese team discovered was that higher levels of SDF-1 may induce the subchondral bone abnormal changes in osteoarthritis and inhibition of SDF-1 signaling could be a potential therapeutic approach for osteoarthritis.

In other words, the classic problems of joint inflammation. SDF-1 is causing too much inflammation and sending signals to create bone leading to the development of bone spurs. Regulating this inflammation can help the patient with joint deterioration. Stem cells play a role.1

Stem cells regulate inflammation

Over now to Germany where doctors are looking for alternatives to knee replacement surgery. The difficulty in doctors determining the difference between regenerative treatments and non-regenerative conservative care is not only apparent but their recommended use is contraindicated to each other. Treatments that create a regenerative inflammatory response that rebuilds tissue are given following anti-inflammatory treatments.

• • • Injections to include corticosteroids, hyaluronic acid, blood-derived products such as Platelet Rich Plasma Therapy, mesenchymal stem cells; are considered the final option for conservative therapy, if systemic pharmaceutical interventions are unsuccessful.2

Treatments such as Platelet Rich Plasma, Stem Cell Therapy, and Prolotherapy are thought of, if thought of at all, after the use of anti-inflammatories and painkillers derail and impede the natural healing process of the body. We damage the inflammatory response healing process when inflammation is needed the most.

In March 2017, researchers in Italy published new research address this concern. Here is what they said:

• • • Although articular cartilage is the target of osteoarthritis, its deterioration is not always clearly associated with patient symptoms. (In other words you can have bone on bone, no cartilage, with no knee pain). Because a functional interaction between cartilage and bone is crucial, the pathophysiology of osteoarthritis and its treatment strategy must focus also on subchondral bone.
    • The Italian researchers then investigated whether adipose-derived stromal cells (ASCs – fat stem cells) injected into a joint at two different concentrations could prevent subchondral bone damage after the onset of mild osteoarthritis in a rabbit knees.
    • Conclusion: “We found that (adipose stem cells) promoted cartilage repair and helped counteract the accelerated bone turnover (degeneration) that occurs with osteoarthritis.9

In supportive research:

• • • Doctors in Mexico find that stem cells can accelerate healing of bone fractures of the jaw bone by nearly 40%.7
    • Doctors at Cambridge University Hospitals in the United Kingdom show promising results regarding the use of stem cells and various growth factors in the treatment of bone fractures and bone non-unions.8

In other new research on fracture healing and bone repair a team of American and British doctors suggest that:

• • • In fracture healing – the state of inflammation dominates the initial phase, but the ideal magnitude and duration of the process for an optimal outcome remains obscure.
    • Biological response modifiers, such as platelet-rich plasma (PRP) preparations, have been used to reconstitute the desirable early inflammatory state, but the results obtained remain inconclusive.
    • Ongoing research to characterize and quantify the inflammatory response after bone fracture is essential;
    • Non-steroidal anti-inflammatory drugs frequently administered for pain management after trauma fracture (and in surgery) continue to be a cause of concern for a successful bone repair response because they stop the inflammatory healing process.3

The problems pointed out above is that any treatment that relies on the inflammatory process needs an expert in inflammation to monitor healing.

Independent of this research comes findings from Iranian doctors who tested the effectiveness of Platelet Rich Plasma on the repair of large bone defects.

• • • Successful healing of large bone defects is a complicated phenomenon because the body’s natural ability often fails to effectively repair the large bone defects. (The body cannot generate enough inflammation to repair the bone.)

The researchers here are calling for new treatments  to increase the quality and accelerate bone healing. They conclude that Platelet concentrates (PRP) in different forms can be considered an attractive option for such purpose because Platelets are a natural source of growth factors, and cytokines (the cells that comprise the healing signalling communication system), and other healing factors.

Here is their opinion:

• • • As the effectiveness of PRP is dependent on various factors, the outcome of PRP therapy is variable and unpredictable in orthopedic patients. 4

Variability based on levels of expertise and doctor experience. In research we often cite a recent article in Orthopedics Today that warns against the high degree in variability among practitioners who use Platelet Rich Plasma (PRP). The main concerns are lack of standardization in treatment regimes and formula concentration.5

Doctors in China have recognized this. Here is their research:

• • • Normal wound healing is a well-orchestrated process of inflammatory response, cell proliferation, and tissue remodeling.
    • However, this orderly and precise process is impaired in chronic wounds. A series of complicated pathogenic factors, including enhanced inflammatory response (too much uncontrolled inflammation), poor cell proliferation (the opposite of the healing inflammatory process of Prolotherapy), restrained angiogenesis (new blood vessels to carry healing factors), restricted collagen deposition (no cartilage building or repair), and infection, contribute to the failure of healing of chronic wound.
    • The application of platelet-rich plasma (PRP) has been explored as a treatment for chronic wounds as it can balance wound microenvironment for promoting wound healing.
    • PRP can modulate the inflammatory mediators, growth factors, and cytokines, etc. to correct abnormal biological events and disorderly molecular environment of cell migration and proliferation, and thus promote wound healing appropriately.
    • Yet, the mechanism of PRP in promoting healing of chronic wound is still not elaborated, and the clinical application of PRP needs to be standardized as soon as possible.6

Here again, the problems pointed out above is that any treatment that relies on the inflammatory process needs an expert inflammationist.

1 Chen Y, Lin S, Sun Y, Guo J, Lu Y, Suen CW, Zhang J, Zha Z, Ho KW, Pan X, Li G. Attenuation of subchondral bone abnormal changes in osteoarthritis by inhibition of SDF-1 signaling. Osteoarthritis and Cartilage. 2017 Jun 30;25(6):986-94. [Pubmed] [Google Scholar]

2 Wehling P, Moser C, Maixner W. How does surgery compare with advanced intra-articular therapies in knee osteoarthritis: current thoughts. Therapeutic Advances in Musculoskeletal Disease. 2016;8(3):72-85. [Pubmed]

3.Giannoudis PV, Hak D, Sanders D, Donohoe E, Tosounidis T, Bahney C. Inflammation, Bone Healing, and Anti-Inflammatory Drugs: An Update. J Periodontol. 2015 Sep 14:1-14. [Pubmed]

4. Oryan A, Alidadi S, Moshiri A. Platelet-rich plasma for bone healing and regeneration. Expert Opin Biol Ther. 2015 Nov 11. [Pubmed]

5  “Platelet-rich plasma promises pain relief and healing, but remains controversial” Orthopedics Today. Web. April 2013. Accessed April 29 2013. [Orthopedics Today]

6. Liu C, Zhang H. Advances in the research of promoting healing of chronic wound with platelet-rich plasma 2014 Oct;30(5):433-6. [Pubmed]

7. Castillo-Cardiel G, López-Echaury AC, Saucedo-Ortiz JA, Fuentes-Orozco C, Michel-Espinoza LR, Irusteta-Jiménez L, Salazar-Parra M, González-Ojeda A. Bone regeneration in mandibular fractures after the application of autologous mesenchymal stem cells, a randomized clinical trial. Dent Traumatol. 2016 Aug 11. [Pubmed]

8. Sinclair KL, Mafi R, Mafi P, Khan W. Mesenchymal stem cells and growth factors used for bone formation, fracture healing and non-unions- A systematic review. Curr Stem Cell Res Ther. 2016 Jun 13. [Pubmed]

9. Parrilli A, Giavaresi G, Ferrari A, Salamanna F, Desando G, Grigolo B, Martini L, Fini M. Subchondral bone response to injected adipose-derived stromal cells for treating osteoarthritis using an experimental rabbit model. Biotech Histochem. 2017 Mar 20:1-11. [Pubmed]