Growing Taller with Synovium Derived Stem Cells

Earlier, we learned that osteophytes can form from synoium derived stem cells.  This is why it is speculated that LSJL makes your bones grow wider more easily than it does make your bones grow longer.  The synovial cavities are more easily compressible than bone and thus it is easier to increase hydrostatic pressure.  At any point where the hydrostatic pressure is sufficient to induce chondrogenic differentiation in the bone marrow it should also be sufficient to induce chondrogenic differentiation in the synovium.

However, articular cartilage has long been regarded as difficult and slow to heal due to the lack of vascularity of cartilage.  The microfracture technique is used to allow bone marrow to seep into the articular cartilage.  So if there are stem cells in the synovium why doesn't the articular cartilage heal more efficiently?  How can we use the stem cells in the synovium to help us grow taller?

Extracellular matrix deposited by synovium-derived stem cells delays replicative senescent chondrocyte dedifferentiation and enhances redifferentiation.

"[We] assess the effect of extracellular matrix (ECM) deposited by synovium-derived stem cells (SDSCs) on articular chondrocyte expansion and maintenance of differentiation status and redifferentiation capacity. Passage 0 (P0) pig articular chondrocytes were expanded for six passages on plastic flasks (Plastic), SDSC-derived ECM (ECM), or substrate switching from either Plastic to ECM (PtoE) or ECM to Plastic (EtoP). Cell morphology, gene expression profiles, and immunophenotypes at each passage were used to characterize differentiation status of expanded cells. Chondrocytes at P0, P2, and P6 were assessed for redifferentiation capacity in a pellet culture system treated with either TGF-β1- or serum-containing medium for 14 days. ECM not only greatly enhanced chondrocyte expansion but also delayed dedifferentiation of expanded chondrocytes. Intriguingly, compared to a dramatic decrease in CD90 + /CD105+ cells and CD90+ cells, CD105+ cells dramatically increased when chondrocytes were plated on Plastic; on the contrary, ECM expansion dramatically increased CD90+ cells and delayed the decrease of CD90 + /CD105+ cells. Interestingly, expanded chondrocytes on ECM also acquired a strong redifferentiation capacity, particularly in the pellets treated with TGF-β1[ECM levels may affect chondrocyte proliferative capacity]. In conclusion, the ratio of CD90 to CD105 may serve as a marker indicative of proliferation and redifferentiation capacity of dedifferentiated chondrocytes{may be possible to manipulate the ratio of cells in the growth plate to grow taller}. ECM deposited by SDSCs provides a tissue-specific three-dimensional microenvironment for ex vivo expansion of articular chondrocytes while retaining redifferentiation capacity."

"Articular cartilage is a unique, hypocellular[contains less than the normal number of cells] and avascular tissue, mostly made of extracellular collagens and proteoglycans (PGs); it has a limited ability to self heal after trauma and degenerative disease"

"Plastic dishes coated with collagen II favored expanded chondrocytes’ chondrogenic potential"<-the more Type II collagen the easier it is to cause chondrogenic differentiation.  Thus it is easier to induce chondrogenic differentiation in already functional growth plates.

"Superficial zone protein (SZP) synthesized by both chondrocytes and synovial cells bordering the joint cavity  provides a protective microenvironment for cartilage progenitor cells at the surface of articular cartilage"<-so the location of cartilage mesenchymal stem cells is at the joint cavity

"A certain subpopulation of multipotent MSCs or progenitor cells in the cartilage tissue [exists] besides terminally differentiated chondrocytes"

"A potential mechanism underlying ECM enhancing chondrocyte proliferation and redifferentiation capacity may be explained by ECM acting through the integrin-mediated extracellular signal-activated kinase (ERK) signal transduction pathway. ECM would interact with chondrocytes through integrins and other signaling receptors, in which [some] integrins were proven to be highly expressed in the cells attaching on 3D ECM. Afterwards, the phosphorylation of ERK1/2 is upregulated by the activated [an] integrin via the Src/Ras/Raf signaling pathway; then the high level of phosphorylated ERK1/2 would enhance TGF-Beta1-mediated redifferentiation of expanded chondrocytes on ECM."<-this is why hyaluronic acid supplementation may make you taller by increasing the ECM proteins in the bone marrow.

So, there are definitely stem cells in the articular cartilage and ECM levels increase chondrogenic potential.  In osteoarthritic or other form of degenerated cartilage there is likely to be very low levels of ECM which is likely why the cartilage does not regenerate properly in those circumstances as the ECM is too low for proper chondrogenic differentiation.

Catabolic factors and osteoarthritis-conditioned medium inhibit chondrogenesis of human mesenchymal stem cells.

"We investigated the effect of a catabolic environment on chondrogenesis in pellet cultures of human mesenchymal stem cells (HMSC). We exposed chondrogenically differentiated HMSC pellets, to IL-1α, TNF-α or conditioned medium derived from osteoarthritic synovium (CM-OAS). IL-1α and TNF-α in CM-OAS were blocked with IL-1Ra or Enbrel respectively{we don't have access to things like Enbrel but many anti-oxidants inhibit TNF-alpha and interleukins}. Chondrogenesis was determined by chondrogenic markers collagen type II, aggrecan and the hypertrophy marker collagen type X on mRNA. Proteoglycan deposition was analyzed by safranin o staining on histology. IL-1α and TNF-α dose-dependently inhibited chondrogenesis{which is why anti-oxidants are important to meet with increased doses of TNF-alpha and IL-1alpha due to mechanical stimuli} when added at onset or during progression of differentiation, IL-1α being more potent than TNF-α. CM-OAS inhibited chondrogenesis on mRNA and protein level but varied in extent between patients. Inhibition of IL-1α partially overcame the inhibitory effect of the CM-OAS on chondrogenesis whereas the TNF-α contribution was negligible. hMSC chondrogenesis is blocked by either IL-1α or TNFalpha alone."

Another reason for the lack of regeneration in articular cartilage could be the presence of inflammatory cytokines.  We can use this in our pursuits for height increase by trying to inhibit these cytokinies.

"Chondrocytes are the only residing cells in cartilage (less than 10% of total cartilage volume in humans) and they function to construct, remodel and maintain the abundant extracellular matrix"<-the cartilagenous growth plate is pure.  Thus when performing something like LSJL which attempts to induce new growth plates by means of hydrostatic pressure we want to try to induce a cartilagenous environment as possible.

"Addition of TGFβ to the chondrogenic differentiation medium was sufficient to induce chondrogenesis"<-we know that LSJL upregulates genes in the TGF-Beta pathway.

"Blocking the inhibitory effect of IL-1 on chondrogenesis was dependent on NF-kappaB translocation to the nucleus. When this was prevented, so was the inhibitory effect. TNF-α inhibition of chondrocytic differentiation was dependent on NF-kappaB mediated posttranscriptional Sox9 and MyoD down-regulation"

"Unfortunately the NF-kappaB pathway is not a suitable blocking candidate as this is crucial for chondrogenesis itself"<-so it's best inhibit IL-1 and TNF-alpha.

Synovial Fluid Progenitors Expressing CD90+ from Normal but Not Osteoarthritic Joints Undergo Chondrogenic Differentiation without Micro-Mass Culture.

"Mesenchymal progenitor cells (MPCs) can differentiate into chondrocytes. Recently, a progenitor cell population has been found within the synovial fluid that shares many similarities with bone marrow MPCs. These synovial fluid MPCs (sfMPCs) [have] a bias for cartilage differentiation [and increased expression of CD44 and UDPGD(an enzyme related to hyaluronan synthesis)]. sfMPCs were isolated from human and canine synovial fluid collected from normal individuals and those with osteoarthritis (human: clinician-diagnosed, canine: experimental) to compare the differentiation potential of CD90+ vs. CD90- sfMPCs, and to determine if CD90 (Thy-1) is a predictive marker of synovial fluid progenitors with chondrogenic capacity in vitro.
sfMPCs were derived from synovial fluid from normal and OA knee joints. These cells were induced to differentiate into chondrocytes.
The CD90+ subpopulation of sfMPCs had increased chondrogenic potential compared to the CD90- population. sfMPCs derived from healthy joints did not require a micro-mass step for efficient chondrogenesis. Whereas sfMPCs from OA synovial fluid retain the ability to undergo chondrogenic differentiation, they require micro-mass culture conditions {So we would want to inject CD90+ stem cells into our epiphysis}."

"The CD90-negative fraction displayed reduced levels of Sox9, Collagen 2 and Aggrecan mRNA"

"whereas whole populations of sfMPCs from normal individuals aggregate and express high levels of chondrogenic markers, whole populations of sfMPCs from OA joints do not aggregate spontaneously, grow only as a monolayer, and express low levels of chondrogenic markers during differentiation"<-does LSJL induce spontaneous chondrogenic aggregation?

"chondrocyte aggregation is mediated by β1-Integrin, while Cadherins seem to play a dominant role in the aggregation of MSCs during chondrogenesis"<-LSJL upregulates ITGBL1 2.436 fold.  Which is integrin-beta like1.

Rejuvenation of chondrogenic potential in a young stem cell microenvironment.

"Autologous cells suffer from limited cell number and senescence during ex vivo expansion for cartilage repair. Here we found that expansion on extracellular matrix (ECM) deposited by fetal synovium-derived stem cells (SDSCs) (FE) was superior to ECM deposited by adult SDSCs (AE) in promoting cell proliferation and chondrogenic potential. Unique proteins in FE might be responsible for the rejuvenation effect of FE while advantageous proteins in AE might contribute to differentiation more than to proliferation. Compared to AE, the lower elasticity of FE yielded expanded adult SDSCs with lower elasticity which could be responsible for the enhancement of chondrogenic and adipogenic differentiation. MAPK and noncanonical Wnt signals were actively involved in ECM-mediated adult SDSC rejuvenation."

"Adult MSCs lack telomerase activity resulting in telomere shortening after serial passaging in vitro"

"decellularized ECM from human adult stem cells, such as SDSCs or BMSCs, exhibited a limited capacity to rejuvenate expanded stem cells' chondrogenic potential."

"compared to up-regulation of p-p38 and p-Jnk, ECM expansion dramatically down-regulated p-Erk; despite the fact that p-Erk bounced back in the cell condensation phase, the lowest level was seen in FE4 pellets; different from the change of p-Erk, ECM expansion yielded ASDSC pellets with a relatively lower level of p-Jnk in the cell condensation phase though no significant difference was found among groups after 10-day chondrogenic induction. Our data also showed that ECM pretreatment down-regulated Wnt3a but up-regulated Wnt5a and Wnt11 in expanded SDSCs; these effects were relayed through cell condensation and chondrogenic differentiation, especially for the Wnt11-mediated non-canonical pathway"

"FE had more fibrillin-2 (76:2), tenascin C{downregulated in LSJL} (259:120), and clusterin (5:0) than AE."<-these proteins may be responsible for the enhanced chondrogenesis.

"enhanced expression of fibrillin-2 and tenascin C has been observed in adults with fibroproliferative conditions, such as wound healing and sclerosis"

"AE had more biglycan{up} (95:37), decorin (95:40), dermatopontin{up} (35:16), elastin (18:2), periostin{up} (400:125), thrombospondin-1{up} (79:6), and TGFβ1 (258:164) than FE."

" AE has more matrix components favoring cell differentiation and apoptosis rather than cell proliferation, which is consistent with the observed differences in elasticity and ECM/collagen architecture, i.e. fibrillar collagens were shifted into the “insoluble” fraction in AE but not in FE."

"in human BMSCs showed that ECM expansion dramatically increased the level of integrin β5 but decreased integrin β1"

" AE expansion yielded higher cell viability (DNA% by day 0) during chondrogenic induction; FE expansion yielded the highest GAG amount per pellet and ratio of GAG to DNA (chondrogenic index) followed by those from AE expansion with PL expansion having the least"

The matrix alterations of LSJL are more consistant to adult ECM than fetal ECM.

So there are stem cells in the synovial joint.  The reason why joints regenerate poorly is likely due to a depleted ECM and the presence of inflammatory cytokines.  We can use these facts to grow taller by taking anti-oxidants to decrease serum levels of inflammatory cytokines.  An adult bone has no Type II collagen in the growth plate and thus dedifferentiation of stem cells into chondrocytes is a potential factor.  To avoid this more frequent application of LSJL throughout the day may be needed to give time for freshly differentiated chondrocytes to secrete ECM before dedifferentiation occurs.  Frequent bursts of hydrostatic pressure plays the role that Type II collagen plays in a unfused growth plate.  In a younger growth plate this may not be necessary as there is already ECM encouraging a chondrogenic micro environment.

Does LSJL put you at risk for osteophytes?

Many have noticed an increase in epiphyseal width but only a small increase in bone length after LSJL loading.  The two methods of increasing epiphyseal width are osteophytes and endochondral ossification.  Endochondral ossification is growth from within and what we are trying to induce with LSJL.  The epiphyseal width growth is more dramatic than with osteophytes and people have not reported decreases in mobility or pain as reported with bony spurs.  Also, there have been no reported long term signs of inflammation from LSJL(people have not reported redness, swelling, or pain).  The sensations of performing joint loading usually go away after 30 seconds.

Understanding osteophytes will help us understand bone growth to a greater degree and will help us eliminate osteophytes as a potential cause of joint width increase.  If we can find that endochondral ossification is the cause of the epiphyseal width increase then we are very close to finding a definitive way to grow taller.

Sports and osteoarthritis.

"Participation in sports that cause minimal joint impact and torsional loading[rotational strain] by people with normal joints and neuromuscular function may cause osteophyte formation, but it has minimal, if any, effect on the risk of osteoarthritis. In contrast, participation in sports that subject joints to high levels of impact and torsional loading increases the risk of injury-induced joint degeneration. People with abnormal joint anatomy or alignment, previous joint injury or surgery, osteoarthritis, joint instability, articular surface incongruity or dysplasia, disturbances of joint or muscle innervation, or inadequate muscle strength have increased risk of joint damage during participation in athletics."

"In a series of investigations of the effects of running without added weight, the results depended on the distance the dogs ran. Moderate running (4 km/d, 5 days a week for 40 weeks) increased cartilage thickness, proteoglycan content, and indentation stiffness. More strenuous running (20 km/d, 5 days a week for 15 weeks) decreased cartilage thickness and proteoglycan content. Longer-term strenuous running (40 km/d for as long as 1 year) decreased cartilage proteoglycan concentration and indentation stiffness and stimulated remodeling of subchondral bone"<-remember that running does not allow for cartilage to replenish proteoglycan content that may be more the cause of the cartilage damage than the load running puts on the joints.  Lateral Joint Loading only loads for 30 seconds to 5 minutes.

"repetitive impact loading is more likely to cause joint degeneration than increased joint use."<-LSJL involves no impact.

Idiopathic chondrolysis of the hip.

Chondrolysis refers to death of chondrocytes usually in the joint.


"The cases of nine patients (eleven hips) with idiopathic chondrolysis of the hip were studied. Seven of the patients were white and two were Hispanic. The age at onset ranged from eight to sixteen years (mean, 11.5 years). Four patients were boys and five were girls. All patients had a decreased passive range of motion of the hip, and radiographic examination showed regional osteoporosis, premature closure of the femoral capital physis, narrowing of the joint space, and lateral overgrowth of the femoral head on the neck. All laboratory examinations were negative for evidence of infection or rheumatoid arthritis. An arthrotomy was done in seven patients. Specimens of the synovial tissue showed no growth on culture, and the histological studies revealed only minimum signs of inflammation[inflammation may not be a prerequisite to bone spurs but rather lack of cartilage may be, the new bone growth does not seem to be derived from synovial tissue] . Histological studies of the articular cartilage were normal. Treatment consisted of administration of acetylsalicylic acid in therapeutic dosages to maintain a blood salicylate level of fifteen to twenty-five milligrams per cent, active non-loading exercise of the hip, protected weight-bearing with crutches, short-term traction to overcome or relieve contractures after biopsy, iliopsoas tenotomy or lengthening in three patients, and an adductor myotomy in one patient. At follow-up, 2.3 to 9.4 years after onset (mean, 6.2 years), six patients had either no symptoms or only minor intermittent discomfort in the hip. On radiographic examination, although these six patients had restoration of the joint space they did have lateral overgrowth of the femoral head (lateral buttressing) and overgrowth of the lateral acetabular margin (lateral osteophyte). In three patients who had disabling pain, joint deterioration was evident on the radiographic examination. One of these patients had a resurfacing arthroplasty to relieve pain." 

In the study there are reports of significant bone overgrowth.  However, this overgrowth is not due to a proliferation of bone spurs.  However, increase in joint width was reported in cases even when physes were closed(however, growth plates are three dimensional so there could still be open regions of the growth plate not detectable on an X-ray).  And the children were followed for a long time thus there physes could have been open earlier.  It's very promising that LSJL can cause overgrowth similar to that noted in developing children.  There's no indication that the increase in joint width could be a cause of pain or joint debilitation.

What is the effect of physical activity on the knee joint? A systematic review.

"We found that the relationships between physical activity and individual joint structures at the knee differ. There was strong evidence for a positive association between physical activity and tibiofemoral osteophytes[osteophyte formation on the articulation connecting the femur and tibia so at the joint area]. However, we also found strong evidence for the absence of a relationship between physical activity and joint space narrowing, a surrogate method of assessing cartilage. Moreover, there was limited evidence from magnetic resonance imaging studies for a positive relationship between physical activity and cartilage volume and strong evidence for an inverse relationship between physical activity and cartilage defects.
This systematic review found that knee structures are affected differently by physical activity. Although physical activity is associated with an increase in radiographic osteophytes, there was no related increase in joint space narrowing, rather emerging evidence of an associated increase in cartilage volume and decrease in cartilage defects on magnetic resonance imaging. Given that optimizing cartilage health is important in preventing osteoarthritis, these findings indicate that physical activity is beneficial, rather than detrimental, to joint health."

There is not a perfect relation between exercise and LSJL as LSJL increases hydrostatic pressure whereas exercise has more impact with lower levels of pressure.  Exercise in general causes osteophytes but without causing cartilage or bone defects.  

"these results suggest that osteophytes are a functional adaption to mechanical stimuli"

"Although osteophytes, bony outgrowths covered by fibrocartilage, are highly associated with cartilage damage, there is also evidence to suggest that osteophytes can develop without explicit injury to cartilage"<-osteophytes are not necessarily an indication of cartilage damage. 

Osteophytes: relevance and biology.

"Osteophytes can contribute both to the functional properties of affected joints and to clinical relevant symptoms. Osteophyte formation is highly associated with cartilage damage but osteophytes can develop without explicit cartilage damage. Osteophytes are mainly derived from precursor cells in the periosteum and growth factors of the TGFbeta superfamily appear to play a crucial role in their induction.[osteophyte formation may be a good thing because it indicates TGFbeta activity which is important for chondrogenesis and therefore endochondral ossification]
Osteophyte formation is an integral component of OA pathogenesis and understanding the biology of osteophyte formation can give insights in the disturbed homeostasis in OA joints."

"Three types of osteophytes are known, the traction spur at the insertion of tendons and ligaments, the inflammatory spur, represented by the syndesmophyte at the insertion of ligaments and tendons to bone as can be seen in ankylosing spondylitis; and the genuine osteophyte or osteochondrophyte (chondro-osteophyte) arising in the periosteum overlying the bone at the junction between cartilage and bone."<-the genuine osteophyte derived from the periosteum may not be a bad thing and may be a functional adaptation to exercise and possibly joint loading.  The increase in joint width may be due to osteophytes and not joint loading.  However, osteophytes are usually smaller and the osteophytes would have to be periosteum derived.  We can't be sure if this is the case.

"Can the development of an osteophyte be considered as an adaptation of a joint to instability or as a result of an altered internal joint milieu resulting in chondrogenesis of precursor cells in the periosteum and synovial lining?"<-if the answer to the latter question is yes that would be very promising to height growth although a previous study showed no signs of synovial tissue growth on culture.

"Osteophytes develop in diarthodial joints. Diarthrodial joints are constrained by a ligamentous structure called the joint capsule. Synovium is a membrane containing macrophages and fibroblast-like cells that cover all the non-cartilaginous surfaces within the capsule. The synovium is separated from the capsule by the subsynovial layer that contains blood vessels and nerves[these blood vessels may contain stem cells that have differentiation potential]. Synovium also covers the periosteum positioned on the outside of the cortical bone in the joint. The periosteum and synovial lining contain cells involved in osteophyte formation."

"Cells in the periosteum covering the bone at the cartilage and bone boundary are stimulated to proliferate. Cells inside the developing osteophyte undergo chondrogenesis and deposit matrix molecules, such as aggrecan, in the tissue. The osteophyte remains covered with a layer of fibroblast-like cells during development. Cells in this layer contribute to the growth of the osteophyte by proliferation and differentiation to chondrocytes inside this layer. The most central chondrocytes further differentiate and hypertrophy. Hypertrophy of the chondrocytes is followed by endochondral ossification, deposition of bone and formation of marrow cavities. A fully developed osteophyte is integrated with the original subchondral bone and still shows a outer fibrous layer[So it's a part of the bone]. The top of the osteophyte is covered with cartilage expanding the original cartilage surface of the joint" <-so an osteophyte itself is a product of endochondral ossification proving that even if the joint growth is due to endochondral ossification, LSJL still causes endochondral ossification.

Since there is no periosteum lining the longitudinal ends of the bone it's logical that osteophytes do not occur on the longitudinal ends of bones but in the picture you can see that the osteophyte slightly increased the overall bone height.

"cell populations from the synovium can be triggered to form cartilage in vitro and synovium-derived MSC have been shown to be even more efficient in cartilage formation than bone marrow-derived MSC"<-so even without access to periosteum it's possibly to induce endochondral ossification in the bone marrow cavity.

" Transforming growth factor β has been shown to be expressed by human osteophytes"

"Studies have indicated that cartilage can be formed by periosteum even in paralyzed limbs and immobilized joints[although an increase in hydrostatic pressure can be noted in immobilized joints]. This demonstrates that mechanical factors are not indispensable in the process of chondrogenesis but does not proof that the initiation of osteophyte formation is independent of mechanical factors. Most likely mechanical stimuli that are transcribed to biochemical factors on a cellular level or autonomous biochemical stimuli initiate the process of chondrogenesis in residing MSC." 

"Oxygen tension and dynamic fluid pressure have been shown to effect chondrogenesis. Chondrogenesis appears to be, somewhat surprisingly, maximal at oxygen levels of 12–15% and no significant differences were observed in a range between 12 and 45%. Only at very high (90%) and very low (1–5%) oxygen concentrations chondrogenesis was impaired. The actual oxygen levels in the joint are in the low range. Although in vivo chondrogenesis during osteophyte formation takes place at relatively low oxygen levels these levels do not appear to stimulate this process. Dynamic fluid pressure was applied to periosteal explants grown in agarose. Low levels of dynamic fluid pressure enhanced chondrogenesis while high levels totally blocked this process. The authors did not use TGFβ in their culture system to induce chondrogenesis so the observed chondrogenesis was a result of the applied pressure. The applied pressure can have a direct effect on the cellular differentiation, induce chondrogenesis-promoting growth factors or modulate growth factor binding to the cells."<-fluid pressure like that induced by LSJL may cause osteophyte formation as it can cause chondrogenesis.

Osteophyte formation is not necessarily a bad thing and osteophytes can be incorporated directly into bone.  Osteophytes are already encouraged by any physical activity they just form more slowly than with LSJL which applies more pressure directly to the joint.  Fluid pressure can cause chondrogenesis and chondrogenesis can occur directly in synovial tissue so bone can increase in width even if not directly connected to the periosteum.  Therefore, it is likely that LSJL causes osteophyte formation which results in the large increase in joint width noted by some LSJL experimenters.  This does not preclude the possibility of endochondral ossification within the bone and means that growth factors that can cause adult chondrogenesis like TGF-Beta are working properly.  The synovial capsule is much more easily compressible than bone and thus is likely to experience more hydrostatic pressure during joint loading.  Thus osteophyte formation is likely to occur at a greater degree than endochondral ossification in length.


Since Synovium derived stem cells show more chondrogenic potential than bone marrow derived stem cells.  It is likely that a greater amount of stimulus is needed to induce differentiation of bone marrow stem cells into chondrocytes.  This does show however that LSJL is effective in upregulating TGF-Beta and increasing fluid pressure.  More may be needed to induce longitudinal bone growth however.

The pattern of vertebral osteophyte development in a South African population

"Vertebral osteophytosis is recognised by outgrowths of bone on the margins of the vertebral body. These spurs have been shown to increase with age and are usually caused by increased spinal pressure. The purpose of this paper is to describe the pattern and severity of osteophyte development in the vertebral columns of male and female South Africans. A total of 101 male and 117 female morphologically normal vertebral columns were investigated. Osteophytes were visually assessed and scored between 0 (no osteophytosis present) and 4 (osteophytes fused together). The highest frequency and degree of projections was on C5, T11, T12, L3, L4 and L5, whereas the lowest frequency was observed on T2 and L1 in females and T2 in males. In both the cervical and lumbar regions, osteophyte development was significantly more pronounced in males than females. Possible reasons for differential osteophytic development throughout the vertebral column include the position of the vertebrae in relation to the line of gravity, mobility of the joint and weight bearing. A description of the normal pattern of osteophytic development across the spine is of great importance for the future development of reliable age-at-death techniques for South African groups."

" Osteophytes start to project horizontally from the vertebral body. 3: Body protrusions curving up or down."

Osteophyte formation in experimental bipedal rats

"The higher pressure imposed on the vertebrae by the erect posture probably explained the greater development of osteophytes in the bipedal groups. The results of the present study seem to give further support to the conception that osteophytes develop as a consequence of pressure exerted on the spine and as a protective mechanism."

Mechanically-induced osteophyte in the rat knee

"Eighteen mature rats received one single impact load of 53 N (30 MPa) to the periosteum of the experimental medial femoral condyles. Contralateral knees were used as controls. Animals were sacrificed at 24 h, 3, 6 and 9 weeks post-impact. Distal femurs were harvested and prepared for histology. Hematoxylin and Eosin, and Masson's trichrome stained slides were examined by light microscopy. Nuclear density was quantified to assess the tissue reaction.

Results

24 h: The synovium membrane, fibrous and cambium periosteum were damaged. Blood infiltration pooled in the impacted medial collateral ligament (MCL) region. Week 3: A cartilaginous tissue spur, chondrophyte, was found in every rat at the impacted site of the MCL. Chondrophytes were composed of fibrocartilage and cartilage matrix, with signs of cartilage mineralization and remodelling activity. Week 6: Chondrophytes presented signs of more advanced mineralisation, recognized as osteophytes. Week 9: Osteophytes appeared to be more mineralized with almost no cartilage tissue.

Conclusions

Osteophytes can be induced with a single mechanical impact applied to the periosteum in rat knees. These data indicate that a moderate trauma to the periosteal layer of the joint may play a role in osteophyte development."

"Osteophytes are thought to develop from cells found in the periosteum"

"periosteal cells are sensitive to mechanical strain to increase cell division"

"These progenitor cells proliferate and differentiate into osteoblastic or chondroblastic lineage cells for intramembranous or endochondral ossification."

"in distraction osteogenesis (DO), a third ossification type has been observed: the transchondroid ossification, characterized as a direct ossification of fibrous tissue"

"A newly formed cartilaginous tissue formation was observed. The growth plate line was observed to project into this structure."

"A cartilaginous tissue formation was observed at different degree on every experimental joint."

"24 h after the impaction, blood infiltration was noticed at the site of impact and appeared to pool in the region adjacent to the enthesis of the MCL, where an osteo-cartilaginous metaplastic tissue outgrowth was found{abnormal}."

" Osteophytes can be mechanically induced with a single load impact of 53 N applied onto the periosteum in rat knees. It was also observed that osteophytes can develop without other signs of osteoarthritis"