ObjectivesIn this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models.MethodsOA was induced in the knee joints of male Wistar rats using transection of the ACL or induction of osteochondral injury. Changes in the percentage of high limb weight distribution (%HLWD) on the operated hind limb were used to determine the pain behaviour in these models. The development of OA was assessed and compared using a histological evaluation based on the Osteoarthritis Research Society International (OARSI) cartilage OA histopathology score.ResultsBoth models showed an increase in joint pain as indicated by a significant (p < 0.05) decrease in the values of %HLWD at one week post-surgery. In the osteochondral injury model, the %HLWD returned to normal within three weeks, while in the ACLT model, a significant decrease in the %HLWD was persistent over an eight-week period. In addition, OA progression was more advanced in the ACLT model than in the osteochondral injury model. Furthermore, the ACLT model exhibited a higher mean OA score than that of the osteochondral injury model at 12 weeks.ConclusionThe development of pain patterns in the ACLT and osteochondral injury models is different in that the OA progression was significant in the ACLT model. Although both can be used as models for a post-traumatic injury of the knee, the selection of appropriate models for OA in preclinical studies should be specified and relevant to the clinical scenario.Cite this article: T. Tawonsawatruk, O. Sriwatananukulkit, W. Himakhun, W. Hemstapat. Comparison of pain behaviour and osteoarthritis progression between anterior cruciate ligament transection and osteochondral injury in rat models. Bone Joint Res 2018;7:244–251. DOI: 10.1302/2046-3758.73.BJR-2017-0121.R2.

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Obesity has been linked to metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Obesity causes a decrease in growth hormone (GH) levels and an increase in insulin levels. Long-term GH treatment increased lipolytic activity as opposed to decreasing insulin sensitivity. Nonetheless, it is possible that short-term GH administration had no impact on insulin sensitivity. In this study, the effect of short-term GH administration on liver lipid metabolism and the effector molecules of GH and insulin receptors were investigated in diet-induced obesity (DIO) rats. Recombinant human GH (1 mg/kg) was then administered for 3 days. Livers were collected to determine the hepatic mRNA expression and protein levels involved in lipid metabolism. The expression of GH and insulin receptor effector proteins was investigated. In DIO rats, short-term GH administration significantly reduced hepatic fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) mRNA expression while increasing carnitine palmitoyltransferase 1A (CPT1A) mRNA expression. Short-term GH administration reduced hepatic FAS protein levels and downregulated gene transcription of hepatic fatty acid uptake and lipogenesis, while increasing fatty acid oxidation in DIO rats. DIO rats had lower hepatic JAK2 protein levels but higher IRS-1 levels than control rats due to hyperinsulinemia. Our findings suggest that short-term GH supplementation improves liver lipid metabolism and may slow the progression of NAFLD, where GH acts as the transcriptional regulator of related genes.

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In recent years, a lot of attention has been focused on using adipose‐derived mesenchymal stem cells obtained from infrapatellar fat pad (IPFP‐ASCs) for the articular cartilage regeneration. IPFP‐ASCs constructs were previously characterized and demonstrated chondrogenic differentiation potential to produce hyaline like‐cartilage in vitro. However, little is known about the relationship of its regeneration potential and pain associated with osteochondral defect. This study aimed to investigate the effect of implantation of the 3‐Dimensional (3D) cartilage construct of IPFP‐ASCs on the restoration of an articular hyaline cartilage as well as attenuation of pain associated with the cartilage defect in an osteochondral defect rat model. The chondrogenic differentiation potential of the 3D cartilage construct derived from IPFP‐ASCs was determined prior to implantation and at 4, 8 and 12 weeks post‐implantation by gene expression and immunochemistry analysis. Pain‐related behavior was examined weekly up to 8 weeks post‐implantation by using weight‐bearing test. A significant pain‐associated with osteochondral defect was observed in this model in all groups post‐induction; however, this pain can spontaneously resolve within three weeks post‐implantation regardless of implantation of IPFP‐ASCs constructs. The existences of mature chondrocytes as well as a significant (p<0.05) positively immunostained for type II collagen and aggrecan were identified in the implanted site for up to 12 weeks compared to untreated group, indicating the hyaline cartilage regeneration. Overall, this study reported the successful outcome of osteochondral regeneration with scaffold‐free IPFP‐ASCs constructs in an osteochondral defect rat model. Although the implantation of the cartilage construct could not attenuate pain associated with the cartilage defect, it provides novel and interesting insights into the current hypothesis that 3D construct IPFP‐ASCs may have potential benefits as an alternative approach to repair bone and cartilage defect.

Non‐alcoholic fatty liver disease (NAFLD) is one of the characteristics of metabolic syndrome. Most people are facing NAFLD whether they are diagnosed with obesity or not. Additionally, growth hormone (GH) administration could mediate the storage of body fat, including in the liver, as a result of the lipolytic effect. In obese patients, the reduction of GH level has been reported. The long‐term treatment of obesity with GH has been shown to reduce body fat mass as well as its well‐known effect to counteract insulin action, leading to insulin resistance. However, this remains unknown whether the short‐term GH administration can alter the fat storage in the liver while it does not worsen insulin sensitivity. To investigate this hypothesis, the rats were fed with either high‐fat (HF) or standard diet for 6 weeks, resulting in diet‐induced obesity (DIO) or diet‐resistant (DR) rats. The effect of short‐term GH treatment (1 mg/kg, twice daily, subcutaneous injection) was then assessed and compared to saline treatment after 3‐day of GH administration. A glucose tolerance test was performed after GH treatment to assess insulin sensitivity in vivo. After euthanasia, the liver was weighed and collected to measure triglyceride concentration by colorimetric assay. Blood was also collected to determine plasma free fatty acid (FFA) levels for the measurement of the lipolytic activity of GH. The results revealed that the percentage of liver mass was significantly greater in DIO and DR rats compared to control rats (p<0.05). The short‐term GH administration did not alter the percentage of liver weight. For liver triglyceride level, DIO and DR rats had a higher level than that of control rats (p<0.05); however, the liver triglyceride level did not affect by the short‐term GH treatment in all rats. Interestingly, the short‐term GH administration significantly increased plasma FFA only in DR rats (p<0.05). Moreover, the effect of GH significantly improved glucose tolerance especially in DIO rats (p<0.01), whereas it did not significantly affect insulin sensitivity in control and DR rats. Taken together, this study suggested that the short‐term GH administration may influence liver lipid metabolism in DR rats. However, further studies are required to determine whether short‐term GH administration affected liver lipid metabolism by interfering with the gene expression, including lipid uptake, lipid synthesis, and lipid oxidation. Additionally, the mechanisms underlying the effect of the short‐term GH administration on insulin sensitivity remains the subject for further studies.

Osteoarthritis (OA) is a multifactorial disease associated with pathological changes in a wide variety of musculoskeletal tissues, including articular cartilage degeneration, synovitis, ligament tears as well as muscle wasting. Cartilage is known as a predominant pathology, however the association between the pathogenesis of OA around the knee joint tissues and pain is limited. Infrapatellar fat pad (IFP) fibrosis and muscle atrophy are the main features of chronic OA phenomenon that cause joint pain, stiffness and impairment of skeletal muscle, which contributing to locomotor restriction in OA patients. Despite a high prevalence of knee OA, there is still a lack of comprehensive information explaining the interplaying mechanisms among these OA features. Although various animal models of OA have been characterized, none of them can truly represent all aspects of the OA features. Monoiodoacetate (MIA)‐induced OA is one of the most common animal model used in the OA research, in which intra‐articular injection of MIA can lead to articular cartilage destruction and development of pain‐like behaviour. This study aimed to characterize and determine the suitable time point, at which MIA could significantly induce the development of IFP fibrosis and hind limb muscle atrophy in this OA rat model. IFP and soleus muscle were collected for histological analysis at 4 and 8 weeks post‐OA induction. In addition, pain‐related behavior was also evaluated using hind limb weight distribution test. Semi‐quantitative analysis of Masson’s trichrome staining revealed that the percentage of IFP fibrosis area was not significantly different at 4 weeks compared to 8 weeks post‐OA induction. In addition, there was a significant (p<0.05) reduction of soleus muscle fiber cross‐sectional area at 4 and 8 weeks of OA‐induced groups compared to their relative controls; however, the muscle fiber atrophy was more pronounced at 4 weeks compared to 8 weeks. Moreover, there was a significant reduction in the mean values of percent weight borne on the injured hind limb for the OA‐induced group compared to the saline group throughout the study period (p<0.05). Interestingly, pain response significantly reversed at 8 weeks compared to 4 weeks (p<0.001), suggesting that this reversal in pain response could be the contributing factor on alleviation of soleus muscle atrophy under chronic OA pain. These results suggested that at 4 weeks post‐MIA injection is sufficient and suitable period to investigate OA‐related pain, IFP fibrosis and muscle atrophy. Taken together, a MIA‐induced OA rat can be used as a representative model in translational research to understand IFP fibrosis and hind limb muscle atrophy in OA as an integrated musculoskeletal disease.