The management of meniscal injuries remains difficult and challenging. Although several clinical ... more The management of meniscal injuries remains difficult and challenging. Although several clinical options exist for the treatment of such injuries, complete regeneration of the damaged meniscus has proved difficult due to the limited healing capacity of the tissue. With the advancements in tissue engineering and cell-based technologies, new therapeutic options for patients with currently incurable meniscal lesions now potentially exist. This review will discuss basic anatomy, current repair techniques and treatment options for loss of meniscal integrity. Specifically, we focus on the possibility and feasibility of the latest tissue engineering approaches, including 3D printing technologies. Therefore, this discussion will facilitate a better understanding of the latest trends in meniscal repair and regeneration, and contribute to the future application of such clinical therapies for patients with meniscal injuries.
When considering the "joint as an organ", the tissues in a joint act as complementary c... more When considering the "joint as an organ", the tissues in a joint act as complementary components of an organ, and the "set point" is the cellular activity for homeostasis of the joint tissues. Even in the absence of injury, joint tissues have adaptive responses to processes, like aging and menopause, which result in changes to the set point. The purpose of this study in a preclinical model was to investigate age-related and menopause-related changes in knee-joint tissues with the hypothesis that tissues will change in unique ways that reflect their differing contributions to maintaining joint function (as measured by joint laxity) and the differing processes of aging and menopause. Rabbit knee-joint tissues from three groups were evaluated: young adult (gene expression, n=8; joint laxity, n=7; water content, n=8), aging adult (gene expression, n=6; joint laxity, n=7; water content, n=5), and menopausal adult (gene expression, n=8; joint laxity, n=7; water content...
Fibroblasts are the most abundant connective tissue cells and play an important role in wound hea... more Fibroblasts are the most abundant connective tissue cells and play an important role in wound healing. It is possible that faster and scarless wound healing in oral mucosal gingiva relative to skin may relate to the distinct phenotype of the fibroblasts residing in these tissues. Connexin 43 (Cx43) is the most ubiquitous Cx in skin (SFBLs) and gingival fibroblasts (GFBLs), and assembles into hemichannels (HCs) and gap junctions (GJs) on the cell membrane. We hypothesized that SFBLs and GFBLs display distinct expression or function of Cx43, and that this may partly underlie the different wound healing outcomes in skin and gingiva. Here we show that Cx43 distinctly formed Cx43 GJs and HCs in human skin and gingiva in vivo. However, in SFBLs, in contrast to GFBLs, only a small proportion of total Cx43 assembled into HC plaques. Using an in vivo-like 3D culture model, we further show that the GJ, HC, and channel-independent functions of Cx43 distinctly regulated wound healing-related ge...
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, Jan 10, 2018
Microscopic visualization under load of the region connecting ligaments/tendons to bone, the enth... more Microscopic visualization under load of the region connecting ligaments/tendons to bone, the enthesis, has been performed previously; however, specific investigation of individual fibril deformation may add insight to such studies. Detailed visualization of fibril deformation would inform on the mechanical strategies employed by this tissue in connecting two mechanically disparate materials. Clinically, an improved understanding of enthesis mechanics may help guide future restorative efforts for torn or injured ligaments/tendons, where the enthesis is often a point of weakness. In this study, a custom ligament/tendon enthesis loading device was designed and built, a unique method of sample preparation was devised, and second harmonic and two-photon fluorescence microscopy were used to capture the fibril-level load response of the rabbit Achilles tendon and medial collateral ligament femoral entheses. A focus was given to investigation of the mechanical problem of fibril embedment. R...
Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue i... more Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i.e., muscle, bone, tendon, and joints) that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK ...
Articular cartilage does not heal spontaneously due to its limited healing capacity, and thus eff... more Articular cartilage does not heal spontaneously due to its limited healing capacity, and thus effective treatments for cartilage injuries has remained challenging. Since the first report by Brittberg et al. in 1994, autologous chondrocyte implantation (ACI) has been introduced into the clinic. Recently, as an alternative for chondrocyte-based therapy, mesenchymal stem cell (MSC)-based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. In this review, we discuss the latest developments regarding stem cell-based therapies for cartilage repair, with special focus on recent scaffold-free approaches.
Compared to skin, wound healing in oral mucosa is faster and produces less scarring, but the mech... more Compared to skin, wound healing in oral mucosa is faster and produces less scarring, but the mechanisms involved are incompletely understood. Studies in mice have linked high expression of CD26 to a profibrotic fibroblast phenotype, but this has not been tested in models more relevant for humans. We hypothesized that CD26 is highly expressed by human skin fibroblasts (SFBLs), and this associates with a profibrotic phenotype distinct from gingival fibroblasts (GFBLs). We compared CD26 expression in human gingiva and skin and in gingival and hypertrophic-like scar-forming skin wound healing in a pig model, and used three-dimensional cultures of human GFBLs and SFBLs. In both humans and pigs, nonwounded skin contained abundantly CD26-positive fibroblasts, whereas in gingiva they were rare. During skin wound healing, CD26-positive cells accumulated over time and persisted in forming hypertrophic-like scars, whereas few CD26-positive cells were present in the regenerated gingival wounds....
Metabolic diseases such as diabetes mellitus type-II (DM-II) may increase the risk of suffering p... more Metabolic diseases such as diabetes mellitus type-II (DM-II) may increase the risk of suffering painful connective tissue disorders and tendon ruptures. The pathomechanisms, however, by which diabetes adversely affects connective tissue matrix metabolism and regeneration, still need better definition. Our aim was to study the effect of DM-II on expressional changes of neuro- and angiotrophic mediators and receptors in intact and healing Achilles tendon. The right Achilles tendon was transected in 5 male DM-II Goto-Kakizaki (GK) and 4 age-matched Wistar control rats. The left Achilles tendons were left intact. At week 2 post-injury, NGF, BDNF, TSP, and receptors TrkA, TrkB and Nk1 gene expression was studied by quantitative RT-PCR (qRT-PCR) and their protein distribution by immunohistochemistry in intact and injured tendons. The expression of tendon-related markers, Scleraxis (SCX) and Tenomodulin (TNMD), was evaluated by qRT-PCR in intact and injured tendons. Injured tendons of diab...
To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabb... more To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility. On days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair. RabPXL01 in HA was administered locally around the repaired tendons, and mRNA expression was compared with untreated repaired tendons and tendon sheaths. We observed, at all time points, increased expression of PRG4 mRNA in tendons treated with rab...
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, Mar 3, 2016
Post-traumatic osteoarthritis (PTOA) development is often observed following traumatic knee injur... more Post-traumatic osteoarthritis (PTOA) development is often observed following traumatic knee injuries involving key stabilising structures such as the cruciate ligaments or the menisci. Both biomechanical and biological alterations that follow knee injuries have been implicated in PTOA development, although it has not been possible to differentiate clearly between the two causal factors. This review critically examines the outcomes from pre-clinical lapine and ovine injury models arising in the authors' laboratories and differing in severity of PTOA development and progression. Specifically, we focus on how varying severity of knee injuries influence the subsequent alterations in kinematics, kinetics, and biological outcomes. The immediate impact of injury on the lubrication capacity of the joint is examined in the context of its influence on biomechanical alterations, thus linking the biological changes to abnormal kinematics, leading to a focus on the potential areas for interv...
Inflammatory diseases and conditions can arise due to responses to a variety of external and inte... more Inflammatory diseases and conditions can arise due to responses to a variety of external and internal stimuli. They can occur acutely in response to some stimuli and then become chronic leading to tissue damage and loss of function. While a number of cell types can be involved, mast cells are often present and can be involved in the acute and chronic processes. Recent studies in porcine and rabbit models have supported the concept of a central role for mast cells in a "nerve-mast cell-myofibroblast axis" in some inflammatory processes leading to fibrogenic outcomes. The current review is focused on the potential of extending aspects of this paradigm into treatments for multiple sclerosis and endometriosis, diseases not usually thought of as having common features, but both are reported to have activation of mast cells involved in their respective disease processes. Based on the discussion, it is proposed that targeting mast cells in these diseases, particularly the early p...
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society, 1999
In this review article, we discuss current data and concepts concerning the molecular biology and... more In this review article, we discuss current data and concepts concerning the molecular biology and biomechanics of both normal and healing ligaments in a rabbit model. Data is presented from light microscopy, transmission electron microscopy, molecular biology (RT-PCR), and biomechanical measurements (laxity, stress at failure, modulus, and static creep) or normal, pregnant and healing rabbit medial collateral ligaments. 'Flaws' in scar matrix, smaller-than-normal diameter collagen fibrils, and failure of collagen cross-link maturation may be particularly important deficiencies which appear to be related to ligament scar weakness and perhaps to scar creep. The mechanical behaviours of both normal and healing ligaments are altered by relative states of joint motion and normal ligaments are affected by systemic hormones (particularly during pregnancy). Molecular analysis of ligaments and ligament scars, combined with ongoing morphological and biomechanical studies of ligament s...
Corneal thickness and curvature are reported to be influenced by hormonal changes associated with... more Corneal thickness and curvature are reported to be influenced by hormonal changes associated with menstrual cycle, pregnancy, or menopause. However, the molecular mechanisms leading to these alterations are not clearly understood. The present study focuses on gene expression patterns (mRNA levels) in corneal tissues following surgically induced menopause in an animal model. The impact of lower hormone levels on mRNA levels in corneal tissues after pre-puberty ovariohysterectomy (OVX) was compared to that in skeletally mature adult animals. Skeletally mature adult female rabbits were either left unoperated (control) or were subjected to OVX at 54 weeks of age using an approved protocol. The central (approximately 6 mm) and the peripheral corneal tissues were harvested from normal and OVX rabbits eight weeks after surgery. In a second study, young sexually immature rabbits at eight weeks of age were subjected to OVX and corneal tissues were collected when the animals were 22 and 32 we...
Young female athletes experience a higher incidence of ligament injuries than their male counterp... more Young female athletes experience a higher incidence of ligament injuries than their male counterparts, females experience a higher incidence of joint hypermobility syndrome (a risk factor for osteoarthritis development), and post-menopausal females experience a higher prevalence of osteoarthritis than age-matched males. These observations indicate that fluctuating sex hormone levels in young females and loss of ovarian sex hormone production due to menopause likely contribute to observed sex differences in knee joint function and risk for loss of function. In studies of osteoarthritis, however, there is a general lack of appreciation for the heterogeneity of hormonal control in both women and men. Progress in this field is limited by the relatively few preclinical osteoarthritis models, and that most of the work with established models uses only male animals. To elucidate sex differences in osteoarthritis, it is important to examine sex hormone mechanisms in cells from knee tissues ...
Journal of Histochemistry & Cytochemistry, 2009
Oral mucosal wounds heal with reduced scar formation compared with skin. The epithelial integrin ... more Oral mucosal wounds heal with reduced scar formation compared with skin. The epithelial integrin αvβ6 is induced during wound healing, and it can activate fibrogenic transforming growth factor β1 (TGF-β1) and anti-fibrogenic TGF-β3 that play key roles in scar formation. In this study, expression of β6 integrin and members of the TGF-β pathway were studied in experimental wounds of human gingiva and both gingiva and skin of red Duroc pigs using real-time PCR, gene microarrays, and immunostaining. Similar to human wounds, the expression of β6 integrin was induced in the pig wounds 7 days after wounding and remained upregulated >49 days. The αvβ6 integrin was colocalized with both TGF-β isoforms in the wound epithelium. Significantly higher expression levels of β6 integrin and TGF-β1 were observed in the pig gingival wounds compared with skin. Early gingival wounds also expressed higher levels of TGF-β3 compared with skin. The spatio-temporal colocalization of αvβ6 integrin with TGF...
The management of meniscal injuries remains difficult and challenging. Although several clinical ... more The management of meniscal injuries remains difficult and challenging. Although several clinical options exist for the treatment of such injuries, complete regeneration of the damaged meniscus has proved difficult due to the limited healing capacity of the tissue. With the advancements in tissue engineering and cell-based technologies, new therapeutic options for patients with currently incurable meniscal lesions now potentially exist. This review will discuss basic anatomy, current repair techniques and treatment options for loss of meniscal integrity. Specifically, we focus on the possibility and feasibility of the latest tissue engineering approaches, including 3D printing technologies. Therefore, this discussion will facilitate a better understanding of the latest trends in meniscal repair and regeneration, and contribute to the future application of such clinical therapies for patients with meniscal injuries.
When considering the "joint as an organ", the tissues in a joint act as complementary c... more When considering the "joint as an organ", the tissues in a joint act as complementary components of an organ, and the "set point" is the cellular activity for homeostasis of the joint tissues. Even in the absence of injury, joint tissues have adaptive responses to processes, like aging and menopause, which result in changes to the set point. The purpose of this study in a preclinical model was to investigate age-related and menopause-related changes in knee-joint tissues with the hypothesis that tissues will change in unique ways that reflect their differing contributions to maintaining joint function (as measured by joint laxity) and the differing processes of aging and menopause. Rabbit knee-joint tissues from three groups were evaluated: young adult (gene expression, n=8; joint laxity, n=7; water content, n=8), aging adult (gene expression, n=6; joint laxity, n=7; water content, n=5), and menopausal adult (gene expression, n=8; joint laxity, n=7; water content...
Fibroblasts are the most abundant connective tissue cells and play an important role in wound hea... more Fibroblasts are the most abundant connective tissue cells and play an important role in wound healing. It is possible that faster and scarless wound healing in oral mucosal gingiva relative to skin may relate to the distinct phenotype of the fibroblasts residing in these tissues. Connexin 43 (Cx43) is the most ubiquitous Cx in skin (SFBLs) and gingival fibroblasts (GFBLs), and assembles into hemichannels (HCs) and gap junctions (GJs) on the cell membrane. We hypothesized that SFBLs and GFBLs display distinct expression or function of Cx43, and that this may partly underlie the different wound healing outcomes in skin and gingiva. Here we show that Cx43 distinctly formed Cx43 GJs and HCs in human skin and gingiva in vivo. However, in SFBLs, in contrast to GFBLs, only a small proportion of total Cx43 assembled into HC plaques. Using an in vivo-like 3D culture model, we further show that the GJ, HC, and channel-independent functions of Cx43 distinctly regulated wound healing-related ge...
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, Jan 10, 2018
Microscopic visualization under load of the region connecting ligaments/tendons to bone, the enth... more Microscopic visualization under load of the region connecting ligaments/tendons to bone, the enthesis, has been performed previously; however, specific investigation of individual fibril deformation may add insight to such studies. Detailed visualization of fibril deformation would inform on the mechanical strategies employed by this tissue in connecting two mechanically disparate materials. Clinically, an improved understanding of enthesis mechanics may help guide future restorative efforts for torn or injured ligaments/tendons, where the enthesis is often a point of weakness. In this study, a custom ligament/tendon enthesis loading device was designed and built, a unique method of sample preparation was devised, and second harmonic and two-photon fluorescence microscopy were used to capture the fibril-level load response of the rabbit Achilles tendon and medial collateral ligament femoral entheses. A focus was given to investigation of the mechanical problem of fibril embedment. R...
Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue i... more Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i.e., muscle, bone, tendon, and joints) that result from obesity-associated metabolic disturbances are less frequently interrogated. As musculoskeletal diseases can lead to the worsening of MetS, this underscores the imminent need to understand the cause and effect relations between the two, and the convergence between inflammatory pathways that contribute to MSK ...
Articular cartilage does not heal spontaneously due to its limited healing capacity, and thus eff... more Articular cartilage does not heal spontaneously due to its limited healing capacity, and thus effective treatments for cartilage injuries has remained challenging. Since the first report by Brittberg et al. in 1994, autologous chondrocyte implantation (ACI) has been introduced into the clinic. Recently, as an alternative for chondrocyte-based therapy, mesenchymal stem cell (MSC)-based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. In this review, we discuss the latest developments regarding stem cell-based therapies for cartilage repair, with special focus on recent scaffold-free approaches.
Compared to skin, wound healing in oral mucosa is faster and produces less scarring, but the mech... more Compared to skin, wound healing in oral mucosa is faster and produces less scarring, but the mechanisms involved are incompletely understood. Studies in mice have linked high expression of CD26 to a profibrotic fibroblast phenotype, but this has not been tested in models more relevant for humans. We hypothesized that CD26 is highly expressed by human skin fibroblasts (SFBLs), and this associates with a profibrotic phenotype distinct from gingival fibroblasts (GFBLs). We compared CD26 expression in human gingiva and skin and in gingival and hypertrophic-like scar-forming skin wound healing in a pig model, and used three-dimensional cultures of human GFBLs and SFBLs. In both humans and pigs, nonwounded skin contained abundantly CD26-positive fibroblasts, whereas in gingiva they were rare. During skin wound healing, CD26-positive cells accumulated over time and persisted in forming hypertrophic-like scars, whereas few CD26-positive cells were present in the regenerated gingival wounds....
Metabolic diseases such as diabetes mellitus type-II (DM-II) may increase the risk of suffering p... more Metabolic diseases such as diabetes mellitus type-II (DM-II) may increase the risk of suffering painful connective tissue disorders and tendon ruptures. The pathomechanisms, however, by which diabetes adversely affects connective tissue matrix metabolism and regeneration, still need better definition. Our aim was to study the effect of DM-II on expressional changes of neuro- and angiotrophic mediators and receptors in intact and healing Achilles tendon. The right Achilles tendon was transected in 5 male DM-II Goto-Kakizaki (GK) and 4 age-matched Wistar control rats. The left Achilles tendons were left intact. At week 2 post-injury, NGF, BDNF, TSP, and receptors TrkA, TrkB and Nk1 gene expression was studied by quantitative RT-PCR (qRT-PCR) and their protein distribution by immunohistochemistry in intact and injured tendons. The expression of tendon-related markers, Scleraxis (SCX) and Tenomodulin (TNMD), was evaluated by qRT-PCR in intact and injured tendons. Injured tendons of diab...
To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabb... more To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility. On days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair. RabPXL01 in HA was administered locally around the repaired tendons, and mRNA expression was compared with untreated repaired tendons and tendon sheaths. We observed, at all time points, increased expression of PRG4 mRNA in tendons treated with rab...
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, Mar 3, 2016
Post-traumatic osteoarthritis (PTOA) development is often observed following traumatic knee injur... more Post-traumatic osteoarthritis (PTOA) development is often observed following traumatic knee injuries involving key stabilising structures such as the cruciate ligaments or the menisci. Both biomechanical and biological alterations that follow knee injuries have been implicated in PTOA development, although it has not been possible to differentiate clearly between the two causal factors. This review critically examines the outcomes from pre-clinical lapine and ovine injury models arising in the authors' laboratories and differing in severity of PTOA development and progression. Specifically, we focus on how varying severity of knee injuries influence the subsequent alterations in kinematics, kinetics, and biological outcomes. The immediate impact of injury on the lubrication capacity of the joint is examined in the context of its influence on biomechanical alterations, thus linking the biological changes to abnormal kinematics, leading to a focus on the potential areas for interv...
Inflammatory diseases and conditions can arise due to responses to a variety of external and inte... more Inflammatory diseases and conditions can arise due to responses to a variety of external and internal stimuli. They can occur acutely in response to some stimuli and then become chronic leading to tissue damage and loss of function. While a number of cell types can be involved, mast cells are often present and can be involved in the acute and chronic processes. Recent studies in porcine and rabbit models have supported the concept of a central role for mast cells in a "nerve-mast cell-myofibroblast axis" in some inflammatory processes leading to fibrogenic outcomes. The current review is focused on the potential of extending aspects of this paradigm into treatments for multiple sclerosis and endometriosis, diseases not usually thought of as having common features, but both are reported to have activation of mast cells involved in their respective disease processes. Based on the discussion, it is proposed that targeting mast cells in these diseases, particularly the early p...
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society, 1999
In this review article, we discuss current data and concepts concerning the molecular biology and... more In this review article, we discuss current data and concepts concerning the molecular biology and biomechanics of both normal and healing ligaments in a rabbit model. Data is presented from light microscopy, transmission electron microscopy, molecular biology (RT-PCR), and biomechanical measurements (laxity, stress at failure, modulus, and static creep) or normal, pregnant and healing rabbit medial collateral ligaments. 'Flaws' in scar matrix, smaller-than-normal diameter collagen fibrils, and failure of collagen cross-link maturation may be particularly important deficiencies which appear to be related to ligament scar weakness and perhaps to scar creep. The mechanical behaviours of both normal and healing ligaments are altered by relative states of joint motion and normal ligaments are affected by systemic hormones (particularly during pregnancy). Molecular analysis of ligaments and ligament scars, combined with ongoing morphological and biomechanical studies of ligament s...
Corneal thickness and curvature are reported to be influenced by hormonal changes associated with... more Corneal thickness and curvature are reported to be influenced by hormonal changes associated with menstrual cycle, pregnancy, or menopause. However, the molecular mechanisms leading to these alterations are not clearly understood. The present study focuses on gene expression patterns (mRNA levels) in corneal tissues following surgically induced menopause in an animal model. The impact of lower hormone levels on mRNA levels in corneal tissues after pre-puberty ovariohysterectomy (OVX) was compared to that in skeletally mature adult animals. Skeletally mature adult female rabbits were either left unoperated (control) or were subjected to OVX at 54 weeks of age using an approved protocol. The central (approximately 6 mm) and the peripheral corneal tissues were harvested from normal and OVX rabbits eight weeks after surgery. In a second study, young sexually immature rabbits at eight weeks of age were subjected to OVX and corneal tissues were collected when the animals were 22 and 32 we...
Young female athletes experience a higher incidence of ligament injuries than their male counterp... more Young female athletes experience a higher incidence of ligament injuries than their male counterparts, females experience a higher incidence of joint hypermobility syndrome (a risk factor for osteoarthritis development), and post-menopausal females experience a higher prevalence of osteoarthritis than age-matched males. These observations indicate that fluctuating sex hormone levels in young females and loss of ovarian sex hormone production due to menopause likely contribute to observed sex differences in knee joint function and risk for loss of function. In studies of osteoarthritis, however, there is a general lack of appreciation for the heterogeneity of hormonal control in both women and men. Progress in this field is limited by the relatively few preclinical osteoarthritis models, and that most of the work with established models uses only male animals. To elucidate sex differences in osteoarthritis, it is important to examine sex hormone mechanisms in cells from knee tissues ...
Journal of Histochemistry & Cytochemistry, 2009
Oral mucosal wounds heal with reduced scar formation compared with skin. The epithelial integrin ... more Oral mucosal wounds heal with reduced scar formation compared with skin. The epithelial integrin αvβ6 is induced during wound healing, and it can activate fibrogenic transforming growth factor β1 (TGF-β1) and anti-fibrogenic TGF-β3 that play key roles in scar formation. In this study, expression of β6 integrin and members of the TGF-β pathway were studied in experimental wounds of human gingiva and both gingiva and skin of red Duroc pigs using real-time PCR, gene microarrays, and immunostaining. Similar to human wounds, the expression of β6 integrin was induced in the pig wounds 7 days after wounding and remained upregulated >49 days. The αvβ6 integrin was colocalized with both TGF-β isoforms in the wound epithelium. Significantly higher expression levels of β6 integrin and TGF-β1 were observed in the pig gingival wounds compared with skin. Early gingival wounds also expressed higher levels of TGF-β3 compared with skin. The spatio-temporal colocalization of αvβ6 integrin with TGF...
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